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Sample records for monoclonal gammopathies healthy

  1. Monoclonal gammopathy of undetermined significance

    National Research Council Canada - National Science Library

    Kyle, Robert A; Vincent Rajkumar, S

    2006-01-01

    Summary Significant advances have been made in our understanding of the natural history, pathogenesis, mechanisms of progression and prognosis of monoclonal gammopathy of undetermined significance (MGUS...

  2. Monoclonal gammopathy and spurious hypophosphatemia.

    Science.gov (United States)

    Weisbord, Steven D; Chaudhuri, Anita; Blauth, Kathleen; DeRubertis, Frederick R

    2003-02-01

    Spuriously low levels of plasma phosphate have been reported previously in patients with multiple myeloma and polyclonal gammopathy. We report 2 cases of spurious hypophosphatemia in patients with elevated concentrations of serum monoclonal immunoglobulins, 1 of whom had monoclonal gammopathy of undetermined significance and the other multiple myeloma. Plasma phosphate concentrations were measured using nondeproteinized and deproteinized plasma samples from patients with monoclonal gammopathies. In 2 patients with monoclonal gammopathy, the levels of plasma inorganic phosphate were reported as <1.0 mg/dL when the phosphate concentration was determined using an analyzer that employs nondeproteinized plasma. When the samples were reanalyzed using a laboratory method that removes serum proteins, normal or elevated concentrations of phosphate were found. Plasma levels of phosphate in 4 other patients with monoclonal gammopathy were normal by both methods. These data confirm previous reports that spurious hypophosphatemia occurs in some patients with increased levels of serum monoclonal immunoglobulins when laboratory methods using nondeproteinized samples are employed. The occurrence of unusually low plasma phosphate concentrations in patients without symptoms or clinically apparent causes of hypophosphatemia should alert physicians to search for monoclonal gammopathy.

  3. Corneal Densitometry for Quantification of Corneal Deposits in Monoclonal Gammopathies.

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    Enders, Philip; Holtick, Udo; Schaub, Friederike; Tuchscherer, Armin; Hermann, Manuel M; Scheid, Christoph; Cursiefen, Claus; Bachmann, Björn O

    2017-04-01

    To assess the capability of Scheimpflug-based densitometry of the cornea to quantify light chain deposits in patients with active monoclonal gammopathies. This is a case-control study in which data from a leading tertiary university center in myeloma care were analyzed. Ten eyes of 5 patients with monoclonal gammopathy and 26 eyes of 13 healthy controls undergoing clinical evaluation and Scheimpflug-based measurements were included in the study. The main outcome measures were densitometry data of the 4 corneal layers-anterior layer (AL), central layer (CL), posterior layer, and total layer (TL)-in 4 different annuli (central annular zone 0-2 mm, intermediate annular zone 2-6 mm, peripheral annular zone 6-10 mm, and total annular zone 0-12 mm). In 8 eyes of 4 patients with IgG-based gammopathy, corneal light backscatter was highest in the AL and decreased with increasing corneal depth. The peripheral annular zone showed a higher densitometry value compared with the corneal center. Compared with healthy controls, the AL (P < 0.001), the CL (P < 0.001), and the TL (P < 0.001) had significantly higher corneal light backscatter in patients with gammopathy in the total and the peripheral annular zones. In one patient with predominantly IgA-based disease, corneal light backscatter was not elevated. Scheimpflug-based densitometry of the cornea is able to quantify opacification by immunoglobulin G light chain deposits in monoclonal gammopathies. This noninvasive technique can complement presently used in vivo confocal microscopy and corneal photography to objectivize corneal changes. Densitometry might allow monitoring of corneal immunoglobulin deposits in follow-up examinations.

  4. Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.

    Science.gov (United States)

    Willrich, Maria A V; Murray, David L; Kyle, Robert A

    2017-05-04

    Monoclonal gammopathies (MG) are defined by increased proliferation of clonal plasma cells, resulting in a detectable abnormality called monoclonal component or M-protein. Detection of the M-protein as either narrow peaks on protein electrophoresis and discrete bands on immunofixation is the defining feature of MG. MG are classified as low-tumor burden disorders, pre-malignancies and malignancies. Since significant disease can be present at any level, several different tests are employed in order to encompass the inherent diverse nature of the M-proteins. In this review, we discuss the main characteristics and limitations of clinical assays to detect M-proteins: protein electrophoresis, immunofixation, immunoglobulin quantitation, serum free light chains and heavy-light chain assays, as well as the newly developed MALDI-TOF mass spectrometric methods. In addition, the definitions of the pre-malignancies monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), as well as monoclonal gammopathy of renal significance (MGRS) are presented in the context of the 2014 international guidelines for definition of myeloma requiring treatment, and the role of the laboratory in test selection for screening and monitoring these conditions is highlighted. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  5. Monoclonal gammopathy with both nemaline myopathy and amyloid myopathy.

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    Wang, Min; Lei, Lin; Chen, Hai; Di, Li; Pang, Mi; Lu, Yan; Lu, Lu; Shen, Xin-Ming; Da, Yuwei

    2017-10-01

    Monoclonal gammopathies due to plasma cell dyscrasias can induce diverse rare neuromuscular disorders. Deposition of monoclonal antibody light chains in skeletal muscle causes amyloid myopathy. Monoclonal gammopathy is occasionally associated with sporadic late-onset nemaline myopathy. Here we report a monoclonal gammopathy patient with both sporadic late-onset nemaline myopathy and amyloid myopathy. The diagnoses were based on immunofixation electrophoresis of urine, and serum for free light chain assay, Congo red staining and Thioflavin S staining of muscle biopsies, as well as immunohistochemical staining and electron-microscopic observation. Nemaline myopathy and amyloid myopathy can present in the same patient with monoclonal gammopathy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Immunological evidence of monoclonal gammopathy in North India: a hospital based study

    Directory of Open Access Journals (Sweden)

    Kalpana Singh

    2010-08-01

    Full Text Available Kalpana Singh1, Bhawna Singh2, Sarika Arora2, Alpana Saxena11Department of Biochemistry, Maulana Azad Medical College and LN Hospital, New Delhi, India; 2Department of Biochemistry, GB Pant Hospital, New Delhi, IndiaBackground: Monoclonal gammopathy of unknown significance (MGUS is a condition in which a paraprotein is found in the blood during standard laboratory tests. It is age-related and characterized by accumulation of bone marrow plasma cells derived from a single abnormal clone. The aim of this study was to investigate the pattern of MGUS in North Indian urban population.Methods: Serum and urine samples were collected from 320 suspected cases of gammopathy, were analyzed by sensitive immunological technique based protein electrophoresis followed by immunofixation for detection and type of monoclonal/polyclonal gammopathies. Twenty-five healthy subjects were included as controls.Results: Gammopathies were observed in 38 (11.88% patients. Out of these 7.5% were ¬monoclonal and 4.3% were polyclonal. Overall age of presentation of these monoclonal ¬gammopathies in both sexes was between 21 and 76 years. Gender-related ratio (men:women for these gammopathies was 1:1.18. Predominant heavy chain isotype was IgG (62.5% followed by IgA (37.5%. Among light chains, kappa (κ and lambda (λ chains appeared in 91.6% and 8.4% gammopathies respectively. Paraprotein fractions obtained were IgGκ (58.3%, IgGλ (4.16%, IgAκ (33.3%, and IgAλ (4.16% with 25% samples being positive for Bence Jones proteinuria.Conclusions: Clinical laboratories play an important role in confirming the immunological diagnosis of gammopathies. Determination of nature of paraproteinemia and its associated diseases calls for more extensive studies in India.Keywords: monoclonal gammopathy, immunoelectrophoresis, multiple myeloma, bence jones protein, immunoglobulins

  7. Monoclonal gammopathy associated with heartworm disease in a dog.

    Science.gov (United States)

    de Caprariis, Donato; Sasanelli, Mariateresa; Paradies, Paola; Otranto, Domenico; Lia, Riccardo

    2009-01-01

    A 12-year-old, intact female, mixed Yorkshire terrier was evaluated for syncopal episodes, weakness, decreased appetite, and weight loss. Heartworm disease was diagnosed based on evidence of circulating microfilariae of Dirofilaria immitis on direct examination of blood smears and a positive SNAP heartworm antigen test. An immunoglobulin G (IgG) gammopathy, demonstrated by serum protein electrophoresis, was associated with heartworm disease in this dog. Response to treatment with both an adulticide and the microfilaricide ivermectin included remission of clinical signs and a decrease in the monoclonal gammopathy. To our knowledge, this is the first report of an IgG gammopathy associated with heartworm disease in the dog.

  8. Monoclonal gammopathy in hereditary spherocytosis: Possible pathogenetic relation

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    Schafer, A.I. (Univ. of Chicago); Miller, J.B.; Lester, E.P.; Bowers, T.K.; Jacob, H.S.

    1978-01-01

    Two cases of monoclonal gammopathy in patients with hereditary spherocytosis led us to consider the possible pathogenetic relation between these two disorders. Twelve adult patients with hereditary spherocytosis had significant hypergammaglobulinemia in comparison to normal subjects. Retrospective analysis of previous illness in 140 patients with multiple myeloma showed a significant association between IgA myeloma and previous gallbladder disease. We propose that the chronic reticuloendothelial stimulation due to extravascular hemolysis, possibly potentiated by the inflammation associated with cholelithiasis and cholecystitis, may foster neoplastic transformation of immunocytes in patients with hereditary spherocytosis, ultimately leading to the development of monoclonal gammopathy.

  9. Prevention of progression in monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Rajkumar, S Vincent

    2009-09-15

    Monoclonal gammopathy of undetermined significance (MGUS) is a common premalignant plasma cell proliferative disorder with a lifelong risk of progression to multiple myeloma. Because myeloma is an incurable malignancy, strategies to delay or prevent progression in high-risk patients are of considerable importance.

  10. Prevention of Progression in Monoclonal Gammopathy of Undetermined Significance

    Science.gov (United States)

    Rajkumar, S. Vincent

    2009-01-01

    Summary Monoclonal gammopathy of undetermined significance (MGUS) is a common premalignant plasma cell proliferative disorder with a lifelong risk of progression to multiple myeloma. Since myeloma is an incurable malignancy, strategies to delay or prevent progression in high-risk patients are of considerable importance. PMID:19737944

  11. Monoclonal Gammopathy of Undetermined Significance Disguised as Chronic Neutrophilic Leukemia

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    Monique A Hartley-Brown

    2010-02-01

    Full Text Available A 60-year-old woman with a medical history of diabetes mellitus, osteoporosis, peripheral vascular disease, and hypertension who was otherwise asymptomatic but continued showing elevated neutrophil levels sought a second opinion at our facility. Serum protein immunoelectrophoresis with immunofixation revealed an immunoglobulin A (IgA-κ monoclonal gammopathy concentration of 1305 mg/dL (normal 80-350 mg/dL but relatively normal concentrations of IgG of 840 mg/dL (620-1400 mg/dL and IgM of 36 mg/dL (45-250 mg/dL. Clonal analysis revealed a polyclonal expression pattern in all cell types analyzed. We concluded that our patient’s neutrophilia may have been due to the underlying monoclonal gammopathy. This is the first case in the literature of a patient with monoclonal gammopathy of undetermined significance presenting with neutrophilia, suggestive of chronic neutrophilic leukemia (CNL.  Patients with CNL have a poor prognosis; therefore, it is important to distinguish diagnostically between CNL and the less severe prognosis of monoclonal gammopathy of undetermined significance.

  12. Monoclonal Gammopathy of Undetermined Significance Disguised as Chronic Neutrophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Monique A Hartley-Brown

    2010-02-01

    Full Text Available A 60-year-old woman with a medical history of diabetes mellitus, osteoporosis, peripheral vascular disease, and hypertension who was otherwise asymptomatic but continued showing elevated neutrophil levels sought a second opinion at our facility. Serum protein immunoelectrophoresis with immunofixation revealed an immunoglobulin A (IgA-κ monoclonal gammopathy concentration of 1305 mg/dL (normal 80-350 mg/dL but relatively normal concentrations of IgG of 840 mg/dL (620-1400 mg/dL and IgM of 36 mg/dL (45-250 mg/dL. Clonal analysis revealed a polyclonal expression pattern in all cell types analyzed. We concluded that our patient’s neutrophilia may have been due to the underlying monoclonal gammopathy. This is the first case in the literature of a patient with monoclonal gammopathy of undetermined significance presenting with neutrophilia, suggestive of chronic neutrophilic leukemia (CNL.  Patients with CNL have a poor prognosis; therefore, it is important to distinguish diagnostically between CNL and the less severe prognosis of monoclonal gammopathy of undetermined significance.

  13. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.

    Science.gov (United States)

    Kyle, Robert A; San-Miguel, Jesus F; Mateos, Maria-Victoria; Rajkumar, S Vincent

    2014-10-01

    Monoclonal gammopathy of undetermined significance (MGUS) is characterized by an M spike less than 3 g/dL and a bone marrow containing fewer than 10% plasma cells without evidence of CRAB (hypercalcemia, renal insufficiency, anemia, or bone lesions). Light chain MGUS has an abnormal free light chain (FLC) ratio, increased level of the involved FLC, no monoclonal heavy chain, and fewer than 10% monoclonal plasma cells in the bone marrow. Smoldering multiple myeloma has an M protein of at least 3 g/dL and/or at least 10% monoclonal plasma cells in the bone marrow without CRAB features. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Unusual Manifestations of Monoclonal Gammopathy: I. Ocular Disease

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    Sophia R. Balderman

    2015-07-01

    Full Text Available Essential monoclonal gammopathy is usually an asymptomatic condition, the characteristics of which have been defined over approximately 70 years of study. It has a known population-attributable risk of undergoing clonal evolution to a progressive, symptomatic B-cell neoplasm. In a very small fraction of patients, the monoclonal immunoglobulin has biophysical characteristics that can lead to tissue deposition syndrome (e.g. Fanconi renal syndrome or, by chance, have characteristics of an autoantibody that may inactivate critical proteins (e.g. acquired von Willebrand disease. In this report, we describe the very uncommon forms of ocular injury that may accompany essential monoclonal gammopathy, which include crystalline keratopathy, crystal-storing histiocytosis, hypercupremic keratopathy, and maculopathy. The first three syndromes result from uncommon physicochemical alterations of the monoclonal immunoglobulin that favor crystallization or exaggerated copper binding. The last-mentioned syndrome is of uncertain pathogenesis. These syndromes may result in decreased visual acuity. These ocular findings may lead, also, to the diagnosis of monoclonal gammopathy.

  15. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders

    DEFF Research Database (Denmark)

    van de Donk, Niels W C J; Palumbo, Antonio; Johnsen, Hans Erik

    2014-01-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple...... myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype...... and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk...

  16. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: Recommendations from the European Myeloma Network

    NARCIS (Netherlands)

    N.W.C.J. van de Donk (Niels); A. Palumbo (Antonio); H.E. Johnsen (Hans); M. Engelhardt (Monika); F. Gay (Francesca); P.K. Gregersen (Peter ); R. Hajek (Roman); M. Kleber (Martina); H. Ludwig (Heinz); G. Morgan (Gareth); P. Musto (Pellegrino); T. Plesner (Torben); O. Sezer; E. Terpos (Evangelos); A. Waage (Anders); S. Zweegman (Sonja); H. Einsele (Hermann); P. Sonneveld (Pieter); H.M. Lokhorst (Henk)

    2014-01-01

    textabstractMonoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; lightchain monoclonal gammopathy of undetermined significance of light-chain

  17. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: Recommendations from the European Myeloma Network

    NARCIS (Netherlands)

    N.W.C.J. van de Donk (Niels); A. Palumbo (Antonio); H.E. Johnsen (Hans); M. Engelhardt (Monika); F. Gay (Francesca); P.K. Gregersen (Peter ); R. Hajek (Roman); M. Kleber (Martina); H. Ludwig (Heinz); G. Morgan (Gareth); P. Musto (Pellegrino); T. Plesner (Torben); O. Sezer; E. Terpos (Evangelos); A. Waage (Anders); S. Zweegman (Sonja); H. Einsele (Hermann); P. Sonneveld (Pieter); H.M. Lokhorst (Henk)

    2014-01-01

    textabstractMonoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; lightchain monoclonal gammopathy of undetermined significance of light-chain

  18. Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI Study Group.

    Science.gov (United States)

    Bellaïche, L; Laredo, J D; Lioté, F; Koeger, A C; Hamze, B; Ziza, J M; Pertuiset, E; Bardin, T; Tubiana, J M

    1997-11-01

    A prospective multicenter study. To evaluate the use of magnetic resonance imaging, in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. Although multiple myeloma has been studied extensively with magnetic resonance imaging, to the authors' knowledge, no study has evaluated the clinical interest of magnetic resonance imaging in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. The magnetic resonance examinations of the thoracolumbar spine in 24 patients with newly diagnosed monoclonal gammopathies of unknown significance were compared with those performed in 44 patients with newly diagnosed nontreated multiple myeloma. All findings on magnetic resonance examination performed in patients with monoclonal gammopathies of unknown significance were normal, whereas findings on 38 (86%) of the 44 magnetic resonance examinations performed in patients with multiple myeloma were abnormal. Magnetic resonance imaging can be considered as an additional diagnostic tool in differentiating between monoclonal gammopathies of unknown significance and multiple myeloma, which may be helpful when routine criteria are not sufficient. An abnormal finding on magnetic resonance examination in a patient with monoclonal gammopathies of unknown significance should suggest the diagnosis of multiple myeloma after other causes of marrow signal abnormalities are excluded. Magnetic resonance imaging also may be proposed in the long-term follow-up of monoclonal gammopathies of unknown significance when a new biologic or clinical event suggests the diagnosis of malignant monoclonal gammopathy.

  19. Prevalence of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review

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    Wadhera, Rishi K.; Rajkumar, S. Vincent

    2010-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder that is associated with a lifelong risk of multiple myeloma. We conducted a systematic review of all studies investigating the prevalence and incidence of MGUS in the online database PubMed. The review was conducted from January 6, 2009, through January 15, 2010. The following MeSH search headings were used: monoclonal gammopathy, benign and prevalence; monoclonal gammopathy, benign and incidence; paraproteinemia and prevalence; and paraproteinemia and incidence. Articles were limited to those written in English and published by January 2009. Fourteen studies that met prespecified criteria were included and systematically assessed to identify the most accurate prevalence estimates of MGUS based on age, sex, and race. On the basis of our systematic review, we estimate that the crude prevalence of MGUS in those older than 50 years is 3.2% in a predominantly white population. Studies in white and Japanese populations demonstrate a clear increase in prevalence with age. The prevalence is also affected by sex: 3.7% and 2.9% in white men and women, respectively; and 2.8% and 1.6% in Japanese men and women, respectively. Additionally, MGUS is significantly more prevalent in black people (5.9%-8.4%) than in white people (3.0%-3.6%). We conclude that MGUS is a common premalignant plasma cell disorder in the general population of those older than 50 years. The prevalence increases with age and is affected by race, sex, family history, immunosuppression, and pesticide exposure. These results are important for counseling, clinical care, and the design of clinical studies in high-risk populations. PMID:20713974

  20. Necrobiotic xanthogranuloma associated with a benign monoclonal gammopathy.

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    Burdick, Anne E; Sanchez, Jany; Elgart, George W

    2003-07-01

    Necrobiotic xanthogranuloma (NXG) is a disorder characterized by indurated, yellow-red nodules or plaques, primarily involving the face and, less frequently, the trunk and extremities. NXG may be associated with paraproteinemia, multiple myeloma, and hypertension. Histologically, xanthogranulomatous features with hyaline necrosis or necrobiosis are present. No first-line treatment has been established. This disease is a chronic process, and a patient's prognosis depends on the degree of extracutaneous involvement and the presence of visceral malignancies. We describe a patient with typical cutaneous and histologic findings of NXG with an associated monoclonal gammopathy.

  1. [Polyneuropathy associated with monoclonal gammopathy of undetermined significance].

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    Moth Henriksen, Marie; Kolmos, Eva Brøsted; Abildgaard, Niels; Schrøder, Henrik Daa; Sindrup, Søren

    2012-10-22

    The prevalence of polyneuropathy in patients with monoclonal gammopathy of undetermined significance (MGUS) has been reported to be 10-50%. The majority of patients have a chronic, slowly progressive, distal, symmetric and predominantly sensory polyneuropathy. A caused relationship between polyneuropathy and immunoglobulin (Ig)M MGUS is better established than the relationship between polyneuropathy and IgG/IgA MGUS because of the observed binding of IgM to myelin sheaths and widening of myelin lamellae. In randomized controlled trials plasma exchange, immunosuppressive, rituximab and intravenous Ig have been found to have a clinical meaningful effect.

  2. Laboratory guidelines for the diagnosis and follow-up of patients with monoclonal gammopathies.

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    Bravo García-Morato, M; Padilla-Merlano, B; Nozal, P; Espiño, M; Juárez, C; Villar, L M; López-Trascasa, M

    2016-04-01

    We present guidelines from the Immunochemistry group of the Spanish Society for Immunology that are designed to provide a practical tool for the diagnosis and follow-up of monoclonal gammopathies. We review the clinical and analytical features of various monoclonal gammopathies, international consensus guidelines and techniques used to detect and follow-up monoclonal components. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  3. Feline lymphoplasmacytic stomatitis associated with monoclonal gammopathy and Bence-Jones proteinuria.

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    Lyon, K F

    1994-03-01

    Lymphoplasmacytic stomatitis and gingivitis was diagnosed in an 8-year old female domestic shorthair. The cat had evidence of severe generalized inflammation of the oral cavity. Biopsy samples were evaluated and displayed a lichenoid, interface stomatitis which was predominantly lymphoplasmacytic. Serum protein electrophoresis confirmed a monoclonal gammopathy. Urine protein electrophoresis confirmed Bence-Jones proteinuria. Protein electrophoresis was used to diagnose monoclonal gammopathy (the production of a monoclonal immunoglobulin, or paraprotein, which is associated with a characteristic "M" protein spike on serum electrophoresis). Diseases associated with monoclonal gammopathy are similar in the dog and cat. Alkylating agent chemotherapy is used to rapidly reduce paraprotein concentrations in multiple myeloma. Multiple myeloma is the most common disorder associated with monoclonal gammopathy. This condition is less common in the cat, compared to the dog. This report examines the diagnosis and treatment of multiple myeloma in a cat presenting with severe stomatitis.

  4. Prevalence of monoclonal gammopathy of undetermined significance in Thailand.

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    Watanaboonyongcharoen, Phandee; Nakorn, Thanyaphong Na; Rojnuckarin, Ponlapat; Lawasut, Panisinee; Intragumtornchai, Tanin

    2012-02-01

    Individuals with monoclonal gammopathy of undetermined significance (MGUS) develop multiple myeloma and related malignancies at the rate of 1% per year. Given differences in ethnicity, data on prevalence and risk factors of MGUS in Thai population will be helpful in understanding the pathogenesis of plasma cell disorders and designing an early cancer detection strategy. Subjects of 50 years or older were included. Demographic data and suspected risk factors were collected. Monoclonal proteins were detected using serum protein electrophoresis. Serum was obtained from 3,260 participants; 1,104 males (33.9%) and 2,156 females (66.1%). The median age was 57 years (range 50-93 years). Monoclonal proteins were detectable in 2.3% (95% confidence interval [CI] 1.8-2.8). M spikes were found in gamma- and beta-globulin regions in 50 (1.5%) and 25 (0.8%) subjects, respectively. The prevalence of MGUS in subjects 50-59, 60-69, and 70 years or older was 2.0% (41/1,975), 2.6% (22/851), and 2.8% (12/434), respectively. By multivariate analysis, MGUS was associated with living outside Bangkok (odds ratio 2.25, 95% CI 1.11-4.58). The overall prevalence of MGUS in the Thai population was 2.3%, which was lower than that in Western countries, but comparable to that in Japan.

  5. Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma.

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    Schmitz, Marian F; Otten, Henny G; Franssen, Laurens E; van Dorp, Suzanne; Strooisma, Theo; Lokhorst, Henk M; van de Donk, Niels W C J

    2014-12-01

    In the course of multiple myeloma, patients may develop a M-protein band different from the original: secondary monoclonal gammopathy of undetermined significance. In this retrospective single center analysis, we describe the occurrence and clinical relevance of secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation (post-transplant monoclonal gammopathy of undetermined significance). A total of 138 patients who had undergone 139 allogeneic stem cell transplantations (39.6% in the upfront setting and 60.4% for relapsed multiple myeloma) were included in the study. Sixty-seven (48.2%) patients developed secondary monoclonal gammopathy of undetermined significance, after a median latency of 6.9 months. Secondary monoclonal gammopathy of undetermined significance occurred more often in patients who achieved at least very good partial response after allogeneic stem cell transplantation, compared to partial response or less (54.8% vs. 26.5%; P=0.005). The incidence was also higher in the upfront setting as compared to relapsed disease, or with a sibling donor compared to matched unrelated donor, but less often after T-cell depletion. Importantly, development of post-transplant monoclonal gammopathy of undetermined significance as a time-dependent variable independently predicted for superior progression-free and overall survival (median progression-free survival 37.5 vs. 6.3 months, Pundetermined significance should not be confused with relapse or progression of disease. (Trial registered with trialregister.nl; HOVON 108: NTR 2958.). Copyright© Ferrata Storti Foundation.

  6. Are neurological complications of monoclonal gammopathy of undetermined significance underestimated?

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    Steiner, Normann; Schwärzler, Angelika; Göbel, Georg; Löscher, Wolfgang

    2017-01-01

    Objectives Monoclonal gammopathy of undetermined significance (MGUS) is a premalignancy preceding multiple myeloma (MM) or related disorders. Neurological symptoms caused by the monoclonal immunoglobulins or free light-chains are often associated with a high morbidity. We analyzed the prevalence of neuropathy, clinical features and the long-term outcome in 223 patients (pts.) with MGUS. Patients and Methods Between 1/2005 and 3/2015, 223 adult pts. with MGUS were identified in our database. Results In36/223 pts. (16%) a neuropathy was diagnosed (MGUS associated neuropathy, MGUS-N). 20 pts. (55%) had a distal symmetric axonal neuropathy, 10 pts. (28%) had a chronic inflammatory demyelinating polyneuropathy and 6 pts (17%) a distal acquired demyelinating symmetric polyneuropathy. In MGUS-NN (without neuropathy) and in MGUS-N, progression to smoldering MM, MM or Waldenstrom's macroglobulinemia (WM) occurred in 17% of the pts. The Immunoglobulin subtype was predominantly IgG in MGUS-NN and IgM in MGUS-N and ≥5.5% plasma cells in the bone-marrow predicted progression to MM and AL-amyloidosis in MGUS-NN and to WM in MGUS-N (p<0.05). Conclusion Due to the substantial prevalence of neuropathies, MGUS pts. should be monitored carefully and referred to a specialized center if neurological symptoms occur. PMID:27974705

  7. [Follow-up of serum monoclonal gammopathy at Guadalajara Health Area].

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    Batuecas Mohedano, M; Carballo Alvarez, F; García Menéndez, L

    2006-12-01

    To study the clinical course of patients with a serum monoclonal protein at Guadalajara Health Area. Prospective study of 186 patients with a newly diagnosed monoclonal component. They have been collected during the years 1999 and 2000. The cumulative transformation probability at 43 months was 4.99% for those patients whose monoclonal gammopathy was overlooked, and 2% at 23 months for patients with monoclonal gammopathy of undetermined significance. The cumulative probability of survival for patients with multiple myeloma was 66.7% at 21 months. The conditional mortality rate (patients/months) at 4 years due to haematological disease was 4.48 x 10(-4) for overlooked patients, 0 for diagnosed of monoclonal gammopathy of undetermined significance and 1.388 x 10(-2) for multiple myeloma diagnosed. A non malignant M component must be followed up due to it could increase patients survival rate in relation with transformation in malignant disease.

  8. Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance.

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    Kubiczkova, Lenka; Kryukov, Fedor; Slaby, Ondrej; Dementyeva, Elena; Jarkovsky, Jiri; Nekvindova, Jana; Radova, Lenka; Greslikova, Henrieta; Kuglik, Petr; Vetesnikova, Eva; Pour, Ludek; Adam, Zdenek; Sevcikova, Sabina; Hajek, Roman

    2014-03-01

    Multiple myeloma still remains incurable in the majority of cases prompting a further search for new and better prognostic markers. Emerging evidence has suggested that circulating microRNAs can serve as minimally invasive biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance. In this study, a global analysis of serum microRNAs by TaqMan Low Density Arrays was performed, followed by quantitative real-time PCR. The analyses revealed five deregulated microRNAs: miR-744, miR-130a, miR-34a, let-7d and let-7e in monoclonal gammopathy of undetermined significance, newly diagnosed and relapsed multiple myeloma when compared to healthy donors. Multivariate logistical regression analysis showed that a combination of miR-34a and let-7e can distinguish multiple myeloma from healthy donors with a sensitivity of 80.6% and a specificity of 86.7%, and monoclonal gammopathy of undetermined significance from healthy donors with a sensitivity of 91.1% and a specificity of 96.7%. Furthermore, lower levels of miR-744 and let-7e were associated with shorter overall survival and remission of myeloma patients. One-year mortality rates for miR-744 and let-7e were 41.9% and 34.6% for the 'low' expression and 3.3% and 3.9% for the 'high' expression groups, respectively. Median time of remission for both miR-744 and let-7e was approximately 11 months for the 'low' expression and approximately 47 months for the 'high' expression groups of myeloma patients These data demonstrate that expression patterns of circulating microRNAs are altered in multiple myeloma and monoclonal gammopathy of undetermined significance and miR-744 with let-7e are associated with survival of myeloma patients.

  9. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network.

    Science.gov (United States)

    van de Donk, Niels W C J; Palumbo, Antonio; Johnsen, Hans Erik; Engelhardt, Monika; Gay, Francesca; Gregersen, Henrik; Hajek, Roman; Kleber, Martina; Ludwig, Heinz; Morgan, Gareth; Musto, Pellegrino; Plesner, Torben; Sezer, Orhan; Terpos, Evangelos; Waage, Anders; Zweegman, Sonja; Einsele, Hermann; Sonneveld, Pieter; Lokhorst, Henk M

    2014-06-01

    Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. Copyright© Ferrata Storti Foundation.

  10. Monoclonal gammopathy of undetermined significance: a new proposal of workup.

    Science.gov (United States)

    Mangiacavalli, Silvia; Cocito, Federica; Pochintesta, Lara; Pascutto, Cristiana; Ferretti, Virginia; Varettoni, Marzia; Zappasodi, Patrizia; Pompa, Alessandra; Landini, Benedetta; Cazzola, Mario; Corso, Alessandro

    2013-10-01

    Diagnostic criteria for monoclonal gammopathy of undetermined significance (MGUS) require quantification of bone marrow plasma cells (BMPCs) and skeletal survey to discriminate between MGUS and multiple myeloma (MM). By contrast, recent published guidelines suggest that these procedures could be avoided in the presence of serum monoclonal spike (M-spike) of small amount (≤1.5 g/dL). Aim of this study is to better quantify the risk of missing a diagnosis of MM, not performing bone marrow aspirate and skeletal survey in patients with M-spike ≤ 1.5 g/dL asymptomatic for bone pain. We reviewed data of 2282 patients consecutively observed from January 1974 to December 2010 in our single hematology department. We considered eligible for this study 1271 patients with grade <2 NCI bone pain, confirmed to have an MGUS or an MM after extensive standardized diagnostic workup including bone marrow biopsy, skeletal bone survey and laboratory tests. The risk of finding a BMPC infiltration ≥10% in patients with an M-spike ≤ 1.5 g/dL was very low (7.3%), although significantly different according to IgH isotype (4.7% for IgG vs. 20.5% for IgA). The risk of finding bone lesions with M-spike ≤ 1.5 g/dL was negligible (2.5%), regardless of IgH isotype. In asymptomatic patients with M-spike of small amount (≤1.5 g/dL): (i) BMPC evaluation may be reasonably avoided in patients with IgG M-spike, while should always be part of diagnostic workup in the presence of IgA M-spike and (ii) skeletal survey, less predictive for MM, should not be routinely indicated irrespective of IgH isotype. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Laboratory Characterizations on 2007 Cases of Monoclonal Gammopathies in East China

    Institute of Scientific and Technical Information of China (English)

    Hao Wang; Chunfang Gao; Lingling Xu; Zaixing Yang; Wenjing Zhao

    2008-01-01

    Monoclonal gammopathies are characterized by the presence of monoclonal immunoglobulin in patients with or without evidence of multiple myeloma (MM), macroglobulinemia, amyloidosis (AL), or a related plasma cell proliferative disorder. This study aims to evaluate laboratory diagnostic characters of monoclonal gammopathies and investigates the correlation between monoclonal gammopathies and transforming growth factor β1 (TGFβ1). Immunofixation electrophoresis (IFE), serum protein electrophoresis (SPE), nephelometry and urine light chain ELISA were used for laboratory identification of monoclonal immunoglobulins. Plasma TGFβ1 was detected with double-antibodies ELISA. Lightcycler was used for single nucleotide polymorphism (SNP) analysis. Totally 2,007 cases of monoclonai immunogiobulin (M protein) were identified in 10,682 samples. The isotypes of M protein were IgG type 47.1%, IgA 23.0%, IgM 8.7%, IgD 5.3%, free light chain κ 6.1%, λ 9.8%. In reference to IFE, the coherency of diagnosis was serum light chain ratio (κ/λ) 94.4%, quantitation of lgs 83%, light chain quantitation 80.9%, and urine light chain ratio (κ/λ) 58.0%. Plasma TGFβ1 was elevated significantly compared to normal control. The allelic frequency of codon 10 (C > T) was neither associated with the existence of the M protein nor with the M protein isotype. Monoclonal gammopathies can be identified with the combination of IFE, SPE, Igs quantitaion and urine light chain determination. Although TGFβ1, an important cytokine in immune regulation, was elevated in monoclonal gammopathies, the SNPs in coding region of TGFβ1 gene did not confer susceptibility to the development of monoclonal gammopathies in this study. Cellular & Molecular Immunology. 2008;5(4): 293-298.

  12. Effect on renal function of an iso-osmolar contrast agent in patients with monoclonal gammopathies

    Energy Technology Data Exchange (ETDEWEB)

    Preda, Lorenzo [Division of Radiology, European Institute of Oncology, IRCCS, Milan (Italy); Agazzi, Alberto; Martinelli, Giovanni [Division of Haematology, European Institute of Oncology, IRCCS, Milan (Italy); Raimondi, Sara [Division of Epidemiology and Biostatistics, European Institute of Oncology, IRCCS, Milan (Italy); University of Milan, Department of Occupational Medicin ' ' Clinica del Lavoro Luigi Devoto' ' Section of Medical Statistics and Biometry ' ' GA Maccacaro' ' , Milan (Italy); Lanfranchi, Carla Federica [University of Milan, IRCCS, School of Medicine, Milan (Italy); Passerini, Rita [Unit of Laboratory Medicine, European Institute of Oncology, IRCCS, Milan (Italy); Calvetta, Albania [Nephrology and Dialysis Unit, Istituto Clinico Humanitas, IRCCS, Rozzano, Milan (Italy); Bellomi, Massimo [Division of Radiology, European Institute of Oncology, IRCCS, Milan (Italy); University of Milan, IRCCS, School of Medicine, Milan (Italy)

    2011-01-15

    To assess the safety of the non-ionic iso-osmolar contrast agent iodixanol on renal function in patients with monoclonal gammopathies undergoing CT. We explored the effect of iodixanol on renal function in 30 patients with monoclonal gammopathies and 20 oncological patients with a normal electrophoretic profile (control group). The parameters used to estimate renal function were: serum creatinine, eGFR (determined 24 h before and 48 h after the administration of iodixanol), and urinary excretion of Neutrophil Gelatinase-Associated Lipocalin (NGAL) determined 2 h and 24 h after. Serum creatinine was also determined 1 month after the administration of iodixanol. No significant increase in serum creatinine values were observed in the monoclonal gammopathies group and in 19/20 patients in the control group. Only 1 patient in the control group developed a transient contrast agent-induced nephropathy. We found no statistically significant difference between the two groups regarding the percentage variation from baseline values of serum creatinine, creatinine clearance, NGAL 2 h after, and eGFR. Whereas NGAL at 24 h showed a statistically significant increase in patients with Monoclonal gammopathies. The use of iodixanol appears to be safe in patients with monoclonal gammopathies and an eGFR {>=} 60 ml/min/1.73 mq. (orig.)

  13. Management of Patients With Hepatitis C Virus, Monoclonal Gammopathy of Undetermined Significance, and Multiple Myeloma.

    Science.gov (United States)

    Hannaford, Alisse; Del Bello, David; Leng, Siyang; Chari, Ajai; Perumalswami, Ponni; Dieterich, Douglas; Branch, Andrea

    2017-01-01

    Background and Aim: The vast majority of the 2.7 million individuals in the United States who are currently infected with hepatitis C virus (HCV) were born between 1945 and 1965. The median age of these patients in this particular generation at the time of this writing was 55 years. In the general population, older age is a risk factor for multiple myeloma (MM) and other monogammopathies. As the baby boomer population ages, HCV providers are increasingly likely to encounter HCV-infected patients with a monoclonal gammopathy. Guidelines for managing these patients are needed. Methods: We conducted a detailed case series investigation of 4 HCV-positive patients with MM or a monoclonal gammopathy disorder. Patients were followed at the Mount Sinai Faculty Practice liver clinic. We also performed a detailed review of the literature exploring if there is any known association between HCV, MM, and monoclonal gammopathy. Results and Conclusions: There is no convincing evidence of a causal association between HCV and MM. HCV is linked to type II and type III cryoglobulinemia, specific kinds of monoclonal gammopathies of determinable significance. Whether a link exists between HCV and MM or monoclonal gammopathy of undetermined significance is unclear. Our case series provides the first evidence that modern HCV treatments with direct-acting antivirals can be safely and effectively co-administered with MM chemotherapy.

  14. [Evaluation of the relations between serum proteins electrophoresis and other laboratory tests in monoclonal gammopathies (author's transl)].

    Science.gov (United States)

    Ramacciotti, P G; Lazzari, L; Minardi, P

    1976-03-01

    We have considered interesting to determine monoclonal gammopathies incidence, in 2191 serum proteins electrophoresis performed in our laboratory from January to December 1974. We have found 15 cases of monoclonal gammopathies, some cases combined with Mieloma (3 cases), some other with other with non specific diseases. We have considered the relations between type of gammopathy and other laboratory tests useful for any other diagnose: they are: immunochemical analysis, E.S.R., red and white count, total proteins, Bence Jones protein.

  15. Immune defects in the risk of infection and response to vaccination in monoclonal gammopathy of undetermined significance and multiple myeloma

    NARCIS (Netherlands)

    Tete, Sarah M.; Bijl, Marc; Sahota, Surinder S.; Bos, Nicolaas

    2014-01-01

    The plasma cell proliferative disorders monoclonal gammopathy of undetermined significance (MGUS) and malignant multiple myeloma (MM) are characterized by an accumulation of transformed clonal plasma cells in the bone marrow and production of monoclonal immunoglobulin. They typically affect an older

  16. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study.

    Science.gov (United States)

    Kristinsson, Sigurdur Y; Tang, Min; Pfeiffer, Ruth M; Björkholm, Magnus; Goldin, Lynn R; Blimark, Cecilie; Mellqvist, Ulf-Henrik; Wahlin, Anders; Turesson, Ingemar; Landgren, Ola

    2012-06-01

    No comprehensive evaluation has been made to assess the risk of viral and bacterial infections among patients with monoclonal gammopathy of undetermined significance. Using population-based data from Sweden, we estimated risk of infections among 5,326 monoclonal gammopathy of undetermined significance patients compared to 20,161 matched controls. Patients with monoclonal gammopathy of undetermined significance had a 2-fold increased risk (Pundetermined significance had an increased risk (Pundetermined significance with M-protein concentrations over 2.5 g/dL at diagnosis had highest risks of infections. However, the risk was also increased (Pundetermined significance who developed infections had no excess risk of developing multiple myeloma, Waldenström macroglobulinemia or related malignancy. Our findings provide novel insights into the mechanisms behind infections in patients with plasma cell dyscrasias, and may have clinical implications.

  17. [Monoclonal gammopathy of undetermined significance (MGUS) in Mexican mestizos: one institution's experience].

    Science.gov (United States)

    Ruiz-Delgado, Guillermo J; Gómez Rangel, J David

    2004-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is defined as presence of serum monoclonal protein at a concentration of 3 g per deciliter or less, no monoclonal protein or only moderate amounts of monoclonal light chains in urine, absence of lytic bone lesions, anemia, hypercalemia, and renal insufficiency related with monoclonal protein, and with a proportion of plasma cells in bone marrow of 10% or less. In Caucasian population, MGUS affects about 3% of individuals > 70 years of age, whereas in Mexican mestizos this figure is substantially lower (0.7%); on the other hand, MGUS represents in Mexico only 2.4% of all monoclonal gammopathies. In a total of 9081 individuals studied prospectively at the Centro de Hematología y Medicina Interna de Puebla throughout a 20-year period, 11 patients with MGUS were identified. Median age was 70 years (range 43-83 years). Patients have been followed in periods ranging from 6 to 3270 days (median, 308 days). Two patients evolved into overt multiple myeloma at 308 and 1687 days after diagnosis of MGUS. Overall median survival (SV) of the group has not been reached, whereas 3270 days overall SV is 91%. After discussing underreporting, biasing, and other confounding factors, it would seem that MGUS, like other monoclonal gammopathies, is less frequent in Mexican mestizos than in Caucasians. Routine screening studies to identify the condition should result in increased numbers of patients.

  18. Acquired von Willebrand syndrome in a patient with monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Puronen, Camille E; Josephson, Neil C; Broudy, Virginia C

    2013-06-01

    Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that typically presents as mucocutaneous bleeding in individuals with no personal or family history of bleeding disorder. Here we present a case in which a patient presented with profound epistaxis and was found to have AVWS in the setting of monoclonal gammopathy of undetermined significance (MGUS).

  19. Hepatitis B Associated Monoclonal Gammopathy That Resolved after Successful Liver Transplant

    Directory of Open Access Journals (Sweden)

    P. Sreenivasan

    2009-01-01

    Full Text Available Monoclonal gammopathy of undetermined significance (MGUS has been most commonly associated with diseases like multiple myeloma, Waldenstrom's macroglobulinemia, primary systemic amyloidosis, HIV, and other lymphoproliferative disorders. There has been an isolated report of MGUS in patients coinfected with HIV and Hepatitis B, as the work by Amara et al. in 2006. Here, we report a case of IgA-kappa light chain gammopathy secondary to Hepatitis B infection, which resolved after liver transplantation. To our knowledge, this is the first reported case of M protein spike seen in the context of Hepatitis B infection only.

  20. Diffuse plane xanthomatosis associated with monoclonal gammopathy Xantomatose plana difusa associada a gamopatia monoclonal

    Directory of Open Access Journals (Sweden)

    Aristóteles Rosmaninho

    2011-08-01

    Full Text Available Diffuse plane normolipemic xanthomatosis (DPNX is a rare, non-inherited disease that is often associated with systemic diseases, mainly malignant hematological (especially multiple myeloma or lymph proliferative disorders. The DPNX can precede the appearance of such conditions by several years, so careful follow-up and periodic laboratory examinations are recommended even for patients that seemed to have no underlying disease. We describe a case associated with monoclonal gammopathy. This case shows that dermatological lesions can be the first manifestation of important hematological diseases and so physicians should be familiarized with this entityA xantomatose plana difusa normolipêmica (XPDN é uma dermatose adquirida rara, muitas vezes associada a doenças sistêmicas, nomeadamente neoplasias hematológicas(sobretudo o mieloma múltiplo ou a processos linfoproliferativos. A XPDN pode preceder o aparecimento dessas doenças em vários anos, sendo por isso recomendada uma vigilância clínica e laboratorial periódica, mesmo para os doentes que aparentemente não apresentam uma doença associada. Descrevemos um caso associado à gamopatia monoclonal. Este caso demonstra a importância das manifestações cutâneas como primeira manifestação de doenças hematológicas importantes e por isso os clínicos devem estar familiarizados com esta entidade

  1. Characterization of Monoclonal Gammopathy of Undetermined Significance by Calorimetric Analysis of Blood Serum Proteome

    Science.gov (United States)

    Barceló, Francisca; Cerdà, Joan J.; Gutiérrez, Antonio; Jimenez-Marco, Teresa; Durán, M. Antonia; Novo, Andrés; Ros, Teresa; Sampol, Antonia; Portugal, José

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant proliferative disorder that may progress to multiple myeloma, a malignant plasma cell neoplasia. We evaluated differential scanning calorimetry (DSC) as an experimental tool for differentiating serum samples of MGUS patients from healthy individuals. DSC thermograms can be used for monitoring changes in the serum proteome associated with MGUS. MGUS patients showed great variability in serum thermogram characteristics, which depended on the IgG, IgA or IgM isotypes and/or the κ or λ light chains. Thermogram feature parameters distinguished patients with MGUS from healthy people. Serum samples, named as non-MGUS, were also collected from patients with subjacent immunological pathologies who were discarded of having MGUS through serum immunofixation. They were used to verify the sensitivity of DSC for discriminating MGUS from related blood dyscrasias. Only some DSC thermogram feature parameters differentiated, to a lesser extent, between MGUS and non-MGUS individuals. We contemplate DSC as a tool for early diagnosis and monitoring of MGUS. PMID:25794164

  2. Monoclonal gammopathy-associated pauci-immune extracapillary-proliferative glomerulonephritis successfully treated with bortezomib.

    Science.gov (United States)

    Grundmann, Franziska; Witthus, Marco; Göbel, Heike; Kisner, Tuelay; Siewert, Rainer; Benzing, Thomas; Kurschat, Christine E

    2013-06-01

    Extracapillary-proliferative glomerulonephritis is a rare complication of multiple myeloma. Partial remission of kidney involvement with cyclophosphamide therapy has previously been described. We report the case of a 60-year-old male patient diagnosed with rapidly progressive glomerulonephritis associated with IgG kappa monoclonal gammopathy. His kidney biopsy revealed pauci-immune extracapillary-proliferative glomerulonephritis without cryoglobulinaemia. Treatment with the proteasome inhibitor bortezomib induced rapid clinical and histological remission of his kidney disease. The patient's renal function remained stable on bortezomib maintenance therapy. Our findings suggest that bortezomib is a promising therapeutic approach to ameliorate severe kidney damage in monoclonal gammopathy- and myeloma-associated pauci-immune extracapillary-proliferative glomerulonephritis.

  3. Monoclonal gammopathy-associated pauci-immune extracapillary-proliferative glomerulonephritis successfully treated with bortezomib

    OpenAIRE

    2013-01-01

    Extracapillary-proliferative glomerulonephritis is a rare complication of multiple myeloma. Partial remission of kidney involvement with cyclophosphamide therapy has previously been described. We report the case of a 60-year-old male patient diagnosed with rapidly progressive glomerulonephritis associated with IgG kappa monoclonal gammopathy. His kidney biopsy revealed pauci-immune extracapillary-proliferative glomerulonephritis without cryoglobulinaemia. Treatment with the proteasome inhibit...

  4. Determining the clinical significance of monoclonal gammopathy of undetermined significance: a SEER-Medicare population analysis.

    Science.gov (United States)

    Go, Ronald S; Gundrum, Jacob D; Neuner, Joan M

    2015-03-01

    Clinical guidelines have recommended annual follow-up examinations of most patients with monoclonal gammopathy of undetermined significance (MGUS); however, evidence supporting this practice is lacking. We performed a population-based study to examine the patterns of disease presentation and outcomes of patients with multiple myeloma, Waldenström macroglobulinemia, and lymphoplasmacytic lymphoma (monoclonal gammopathy-associated malignancies) comparing those with or without a previous MGUS follow-up examination. Patients with monoclonal gammopathy-associated malignancy from 1994 through 2007 were identified using the Surveillance, Epidemiology, and End Results-Medicare linked database and divided into 2 cohorts: those with follow-up (MGUS follow-up examination preceding the diagnosis) and those with no follow-up (no such follow-up examination). We compared the outcomes, including the rates of major complications at cancer diagnosis (acute kidney injury, cord compression, dialysis use, fracture, and hypercalcemia) and survival using propensity score adjustment and Cox proportional hazard models. All statistical tests were 2-sided. Of the 17,457 study patients, 6% had undergone MGUS follow-up. After multivariable modeling, the follow-up group had significantly fewer major complications at diagnosis (odds ratio 0.68; 95% confidence interval [CI], 0.57-0.80) and better disease-specific (median, 38 vs. 29 months, P < .001; hazard ratio [HR] 0.85; 95% CI, 0.76-0.94) and overall (median, 23 vs. 19 months, P < .001; HR 0.87; 95% CI, 0.80-0.95) survival. Patients with MGUS follow-up preceding the diagnosis of a monoclonal gammopathy-associated malignancy can experience fewer major complications and have longer survival than those without such follow-up examinations. Future studies replicating our findings in the non-Medicare population and determining the optimal schedule and cost-effectiveness of MGUS follow-up are warranted. Copyright © 2015 Elsevier Inc. All rights

  5. Monoclonal gammopathy of undetermined significance: Using risk stratification to guide follow-up.

    Science.gov (United States)

    Uddin, Zia; Maennle, Diane; Russell, Kimberly; Boltri, John M

    2015-07-01

    Varying combinations of 3 measurable factors determine a patient's risk of progressing toward multiple myeloma and influence monitoring decisions. This review--and accompanying algorithm--can guide your approach. For monoclonal gammopathy of undetermined significance (MGUS) patients at low risk, repeat serum protein electrophoresis (SPE) in 6 months. If no significant elevation of M-protein is found, repeat SPE every 2 to 3 years.

  6. [The value of serum free light chain in differential diagnosis of monoclonal gammopathy of renal significance].

    Science.gov (United States)

    Li, C; Wen, Y B; Li, H; Su, W; Li, J; Cai, J F; Chen, L M; Li, X M; Li, X W

    2017-08-08

    Objective: To investigate the value of serum free light chain (FLC) in differential diagnosis of monoclonal gammopathy of renal significance (MGRS). Methods: Forty-nine hospitalized patients who underwent renal biopsy in Peking Union Medical College Hospital between January 2013 and December 2015 were included. Monoclonal gammopathy was detected by serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE), urine IFE and serum FLC. All patients were classified as MGRS (n=32) and monoclonal gammopathy of undetermined significance (MGUS) (n=17). Results: Renal lesions in MGRS subgroup included light chain amyloidosis (n=24, 75.0%), light chain deposition disease (n=7, 21.9%), and fibrillary glomerulopathy (n=1, 3.1%). Renal diseases in MGUS subgroup included membranous nephropathy (n=10), focal segmental glomerulosclerosi (FSGS) (n=3), diabetic glomerulopathy (n=1), Henoch-Schonlein purpura nephritis (n=1), anti-GBM disease concurrent with membranous nephropathy (n=1) and glomerulomegaly (n=1). Positive number of SPE, serum IFE, urine IFE and abnormal number of serum FLC ratio in MGRS subgroup were 12, 16, 23 and 30, respectively. Positive number of SPE, serum IFE, urine IFE and abnormal number of serum FLC ratio in MGUS subgroup were 11, 17, 6 and 3, respectively. MGRS and MGUS subgroups differed significantly in positive rate of serum IFE (Pvalue for MGRS, which was helpful for differential diagnosis of patients who had contraindication to renal biopsy.

  7. Polyneuropathy associated with monoclonal gammopathy, cause and consequence

    NARCIS (Netherlands)

    Eurelings, Marijke

    2005-01-01

    The relation between monoclonal antibodies and polyneuropathy is best supported for polyneuropathy associated with IgM monoclonal anti-myelin associated glycoprotein (anti-MAG) antibodies. These anti-MAG antibodies are reactive against peripheral nerve autoantigen, thereby causing an autoimmune medi

  8. Non-secretory immunoglobulin E myeloma associated with immunoglobulin G monoclonal gammopathy of undetermined significance

    Directory of Open Access Journals (Sweden)

    Masako Yasuyama

    2012-07-01

    Full Text Available A 68-year old woman came to our hospital with a severe case of anemia. Serum immunoelectropheresis identified a monoclonal immunoglobulin (Ig G and κ protein. The serum IgE level was within the nomal range and the amounts of remaining immuno - globlins were low. On bone marrow aspirate, plasma cells made up 55.5% of nucleated cells and the plasma cells showed positive readings for IgE κ and IgG by immunohistochemistry. Serum immunofixation did not reveal the IgE monoclonal band. She was diagnosed as having non-secretory IgE myeloma with IgG monoclonal gammopathy of undetermined significance. The nature of this rare myeloma will be discussed.

  9. Diagnosis and follow-up of monoclonal gammopathies of undetermined significance; information for referring physicians.

    Science.gov (United States)

    Caers, Jo; Vekemans, Marie-Christiane; Bries, Greet; Beel, Karolien; Delrieu, Vanessa; Deweweire, Anne; Demuynck, Hilde; De Prijck, Bernard; De Samblanx, Hadewijch; Kentos, Alain; Meuleman, Nathalie; Mineur, Philippe; Offner, Fritz; Vande Broek, Isabelle; Van Droogenbroeck, Jan; Vande Velde, Ann; Wu, Ka Lung; Delforge, Michel; Schots, Rik; Doyen, Chantal

    2013-09-01

    The prevalence of monoclonal gammopathy of undetermined significance (MGUS) is generally estimated at 3.4% in the general population over 50 years, and its incidence increases with age. MGUS represents a preneoplastic entity that can transform into multiple myeloma or other lymphoproliferative disorders. The risk of malignant transformation is estimated at 1% per year and persists over time. Predictors of malignant transformation have been identified such as the heavy chain isotype, The level of monoclonal proteins, increasing levels of the monoclonal component during the first years off follow-up, the percentage of bone marrow plasmocytosis, the dosage of serum free light chains, the presence of immunophenotypically abnormal plasma cells, aneuploidy, and the presence of circulating plasma cells. Prognostic scores that combine certain of these factors have been proposed and allow the identification of high-risk patients. Their use could assist in tailoring the care for each patient, based on his/her risk profile.

  10. Diagnosis, risk stratification and management of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.

    Science.gov (United States)

    van de Donk, N W C J; Mutis, T; Poddighe, P J; Lokhorst, H M; Zweegman, S

    2016-05-01

    Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders. IgG and IgA MGUS are precursor conditions of multiple myeloma (MM), whereas light-chain MGUS is a precursor condition of light-chain MM. Smoldering MM (SMM) is a precursor condition with higher tumor burden and higher risk of progression to symptomatic MM compared to MGUS. Assessment of the risk of progression of patients with asymptomatic monoclonal gammopathies is based on various factors including clonal burden, as well as biological characteristics, such as cytogenetic abnormalities and light-chain production. Several models have been constructed that are useful in daily practice for predicting risk of progression of MGUS or SMM. Importantly, the plasma cell clone may occasionally be responsible for severe organ damage through the production of a M-protein which deposits in tissues or has autoantibody activity. These disorders are rare and often require therapy directed at eradication of the underlying clone. Importantly, recent studies have shown that asymptomatic patients with a bone marrow plasma cell percentage ≥60%, free light-chain ratio ≥100, or >1 focal lesion on MRI (myeloma-defining events) have a 80% risk of developing symptomatic MM within 2 years. These patients are now considered to have MM requiring therapy, similar to patients with symptomatic disease. In this review, we provide an overview of the new diagnostic criteria of the monoclonal gammopathies and discuss risk of progression to active MM. We also provide recommendations for the management of patients with MGUS and SMM including risk-adapted follow-up. © 2016 John Wiley & Sons Ltd.

  11. The relationship between hypogammaglobulinemia, monoclonal gammopathy of undetermined significance and humoral immunodeficiency: a case series.

    Science.gov (United States)

    Zemble, Robert Marc; Takach, Patricia A; Levinson, Arnold I

    2011-10-01

    Hypogammaglobulinemia of the non-monoclonal immunoglobulin heavy chain classes has been reported in monoclonal gammopathy of undetermined significance (MGUS) patients. Whether low polyclonal immunoglobulin levels are associated with impaired specific antibody production and whether they represent a risk factor for the development of recurrent bacterial infections have not been established in this population. We determined the frequency of MGUS in patients referred to a tertiary care clinical immunology ambulatory care practice for evaluation of hypogammaglobulinemia, who were assessed for deficits in specific antibody production and the presence of recurrent infections. Of the 133 patients evaluated for hypogammaglobulinemia, 68 were screened for monoclonal gammopathy and 5 were found to have MGUS. Three had MGUS associated hypogammaglobulinemia in the absence of a defining primary immunodeficiency, one possibly had common variable immunodeficiency, and one had an uncertain diagnosis. Thus, MGUS may be uncovered in patients presenting with hypogammaglobulinemia even in those who lack an elevated serum level of IgG, IgM, or IgA.

  12. [The role of the assessment of heavy/light chain pairs of immunoglobulin in monoclonal gammopathies].

    Science.gov (United States)

    Ščudla, Vlastimil; Pika, Tomáš; Minařík, Jiří

    2015-01-01

    The aim of the paper is to inform about the contribution of novel, highly sensitive analytic technique for the assessment of serum immunoglobulins (Hevylite), enabling separate quantitative assessment of heavy/light chain pairs of immunoglobulin (HLC), i. e. the monoclonal ("involved") and polyclonal ("noninvolved") isotype including their ratio (HLC-r) in monoclonal gammopathies. We particularly target the characteristics of this technique, the compari-son of its clinical contribution with standard methods used in the diagnostics, course and the detection of relapse and progression of the disease, as well as the stratification, assessment of therapeutic outcome and prognosis in monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenström´s macroglobulinemia, systemic AL-amyloidosis and some non-Hodgkin lymphomas. Present results show that in comparison with existing routinely used techniques the Hevylite method enriches clinical practice with the assessment of serum levels of "uninvolved" Ig. It enables the evaluation of the depth of "immunoparesis", and the determination of HLC-r index that is needful for the stratification of MM into "risk cohorts". It also contributes to prognostic assessment and improvement of the evaluation of the depth of therapeutic response. In MGUS individuals the HLC-r index provides information about the risk of malignant transformation. We await the results of ongoing validation studies that are expected to provide specific indications for Hevylite technique for MG in routine practice.

  13. Identification of the potential risk factors for monoclonal gammopathy of undetermined significance of progression.

    Science.gov (United States)

    Li, Rong; Du, Juan; Hou, Jian

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder. The etiology of MGUS progression remains unclear and is a current topic of investigation. This review summarizes the essential features of MGUS and the potential risk factors for MGUS of progression. Many clinical studies have been conducted to identify the critical risk markers that play important roles in progression. Some clinical variables, such as immunophenotypic markers and cytogenetic changes, have been recognized as potential risk factors. In this review, we discuss novel insights from recent studies of potential risk factors, and we propose future directions for clinical management and additional studies.

  14. Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma in Older Adults.

    Science.gov (United States)

    Guerard, Emily J; Tuchman, Sascha A

    2016-02-01

    Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are plasma cell disorders of aging. The landscape of the diagnosis and management of MM and MGUS are rapidly changing. This article provides an updated understanding of the clinical presentation, evaluation, diagnosis, and management of older adults with MM and MGUS. Because most oncology providers are not formally trained in geriatric medicine, geriatricians play a key role in providing oncologists with a broader understanding of patient health status in the hope of improving outcomes for older adults with MM.

  15. Monoclonal gammopathy of undetermined significance-making it understandable to patients.

    Science.gov (United States)

    Rule, Pamela; Brant, Jeannine M

    2013-12-01

    Oncology nurses working in ambulatory care often encounter patients with nonmalignant hematologic disorders because the specialties of hematology and oncology are closely entwined. A variety of nonmalignant hematologic disorders can evolve into blood malignancies; therefore, close surveillance of nonmalignant hematologic disorders in an oncology/hematology clinic is important for early detection of malignancy. Monoclonal gammopathy of undetermined significance (MGUS) is one nonmalignant, hematologic disorder that is usually aproblematic; however, it can evolve into a blood malignancy such as multiple myeloma or be associated with other chronic conditions. This article provides an overview of MGUS with a focus on implications for the oncology nurse and patient education.

  16. Association between the delta estimated glomerular filtration rate and the prevalence of monoclonal gammopathy of undetermined significance in Korean males.

    Science.gov (United States)

    Jeong, Tae-Dong; Lee, Woochang; Chun, Sail; Min, Won-Ki

    2014-01-01

    We investigated the association between the reduction in the estimated glomerular filtration rate (eGFR) and the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in Korean males. We enrolled 723 healthy Korean males. Serum creatinine concentration, serum electrophoresis, serum immunofixation, and the serum free light chain assay were performed. We calculated delta eGFR per year (ΔeGFR/yr). The prevalence of MGUS was compared based on the ΔeGFR/yr and age group. Thirteen (1.8%) of 723 participants exhibited the monoclonal band on serum immunofixation. Prevalence of MGUS by age group was 0.00% (0/172 for 40 years), 1.63% (6/367 for 60 years), and 3.80% (7/184 for >60 years). The median decrease in ΔeGFR/yr was 5.3%. The prevalence of MGUS in participants in their 50s with >5.3% decline in ΔeGFR/yr was significantly higher than those with 5.3% decrease in ΔeGFR/yr was similar to that of healthy males in their 60s. Using the rate of reduction in ΔeGFR/yr in healthy Korean males who had their serum creatinine level checked regularly may increase the MGUS detection rate in clinical practice.

  17. Circulating Regulatory T-Cells in Monoclonal Gammopathies of Uncertain Significance and Multiple Myeloma: In Search of a Role

    Directory of Open Access Journals (Sweden)

    Giovanni D’Arena

    2016-01-01

    Full Text Available The frequency and function of regulatory T-cells (Tregs in multiple myeloma (MM are still matter of debate. The percentage and absolute number of circulating Tregs (CD4+CD25+high  densityCD127-/low  density from 39 patients with untreated MM and 44 patients with monoclonal gammopathies of uncertain significance (MGUS were tested and compared with 20 healthy subjects as controls. The mean percentage number of circulating Tregs was 2.1%  ± 1.0 (range 0.75–6.1% in MM patients; 2.1%  ± 0.9 (range 0.3–4.4% in MGUS; and 1.5%  ± 0.4 (range 0.9–2.1% in controls (p ns. Mean absolute number of Tregs was 36.3/μL ± 23.7 (range 6.7–149/μL in MM; 38.8/μL ± 19.1 (range 4.3–87/μL in MGUS; and 39.4/μL ± 12.5 (range 18–63/μL in controls (p ns. After a median follow-up of 38 months, 5 MGUS and 2 smoldering MM (SMM transformed into overt MM; however Tregs number did not predict this evolution. With respect to MM patients and after a median follow-up of 33 months, Tregs did not show any significant correlation with main clinical and laboratory characteristics. Finally, from a functional point of view, Tregs displayed an effective suppressor function, irrespective of disease status. This study indicates that the number of circulating Tregs does not differ in different monoclonal gammopathies and normal subjects and do not correlate with clinical features of MM.

  18. Circulating Regulatory T-Cells in Monoclonal Gammopathies of Uncertain Significance and Multiple Myeloma: In Search of a Role.

    Science.gov (United States)

    D'Arena, Giovanni; Rossi, Giovanni; Laurenti, Luca; Statuto, Teodora; D'Auria, Fiorella; Valvano, Luciana; Simeon, Vittorio; Giudice, Aldo; Innocenti, Idanna; De Feo, Vincenzo; Filosa, Rosanna; Musto, Pellegrino

    2016-01-01

    The frequency and function of regulatory T-cells (Tregs) in multiple myeloma (MM) are still matter of debate. The percentage and absolute number of circulating Tregs (CD4(+)CD25(+high  density)CD127(-/low  density)) from 39 patients with untreated MM and 44 patients with monoclonal gammopathies of uncertain significance (MGUS) were tested and compared with 20 healthy subjects as controls. The mean percentage number of circulating Tregs was 2.1%  ± 1.0 (range 0.75-6.1%) in MM patients; 2.1%  ± 0.9 (range 0.3-4.4%) in MGUS; and 1.5%  ± 0.4 (range 0.9-2.1%) in controls (p ns). Mean absolute number of Tregs was 36.3/μL ± 23.7 (range 6.7-149/μL) in MM; 38.8/μL ± 19.1 (range 4.3-87/μL) in MGUS; and 39.4/μL ± 12.5 (range 18-63/μL) in controls (p ns). After a median follow-up of 38 months, 5 MGUS and 2 smoldering MM (SMM) transformed into overt MM; however Tregs number did not predict this evolution. With respect to MM patients and after a median follow-up of 33 months, Tregs did not show any significant correlation with main clinical and laboratory characteristics. Finally, from a functional point of view, Tregs displayed an effective suppressor function, irrespective of disease status. This study indicates that the number of circulating Tregs does not differ in different monoclonal gammopathies and normal subjects and do not correlate with clinical features of MM.

  19. Circulating Regulatory T-Cells in Monoclonal Gammopathies of Uncertain Significance and Multiple Myeloma: In Search of a Role

    Science.gov (United States)

    Rossi, Giovanni; Laurenti, Luca; Statuto, Teodora; D'Auria, Fiorella; Valvano, Luciana; Simeon, Vittorio; Giudice, Aldo; Innocenti, Idanna; De Feo, Vincenzo; Filosa, Rosanna; Musto, Pellegrino

    2016-01-01

    The frequency and function of regulatory T-cells (Tregs) in multiple myeloma (MM) are still matter of debate. The percentage and absolute number of circulating Tregs (CD4+CD25+high  densityCD127−/low  density) from 39 patients with untreated MM and 44 patients with monoclonal gammopathies of uncertain significance (MGUS) were tested and compared with 20 healthy subjects as controls. The mean percentage number of circulating Tregs was 2.1%  ± 1.0 (range 0.75–6.1%) in MM patients; 2.1%  ± 0.9 (range 0.3–4.4%) in MGUS; and 1.5%  ± 0.4 (range 0.9–2.1%) in controls (p ns). Mean absolute number of Tregs was 36.3/μL ± 23.7 (range 6.7–149/μL) in MM; 38.8/μL ± 19.1 (range 4.3–87/μL) in MGUS; and 39.4/μL ± 12.5 (range 18–63/μL) in controls (p ns). After a median follow-up of 38 months, 5 MGUS and 2 smoldering MM (SMM) transformed into overt MM; however Tregs number did not predict this evolution. With respect to MM patients and after a median follow-up of 33 months, Tregs did not show any significant correlation with main clinical and laboratory characteristics. Finally, from a functional point of view, Tregs displayed an effective suppressor function, irrespective of disease status. This study indicates that the number of circulating Tregs does not differ in different monoclonal gammopathies and normal subjects and do not correlate with clinical features of MM. PMID:27493974

  20. Monoclonal gammopathy of undeterminated significance and endoneurial IgG deposition

    Science.gov (United States)

    Mathis, Stéphane; Franques, Jérôme; Richard, Laurence; Vallat, Jean-Michel

    2016-01-01

    Abstract Background: Monoclonal gammopathy of undeterminated significance is the most common form of plasma cell dyscrasia, usually considered as benign. In rare cases it may have a malignant course, sometimes limited to an organ such as peripheral nerves. Methods: We describe clinical, electrophysiological and pathological findings in a patient presenting a immunoglobulin G (IgG) paraproteinemic polyneuropathy clinically mimicking a chronic inflammatory demyelinating polyneuropathy. Results: Immuno-electron microscopy (immune-EM) demonstrated that the widenings of the myelin lamellae resulted from the infiltration of IgG between a significant number of myelin lamellae (with absence of inflammatory cells in the epineurium, endoneurium, and perineurium, and the lack signs of vasculitis). This patient was finally treated successfully with lenalidomide then mycophenolate mofetil. Conclusions: In polyneuropathies associated to a monoclonal gammopathy, a nerve biopsy may clinch the diagnosis. Immuno-EM may be required to determine the role of the pathological immunoglobulin in the destruction of the peripheral nerve parenchyma. Diagnosis of such a direct involvement of peripheral nerve can endorse more aggressive treatment of real efficiency. PMID:27603395

  1. Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Uruha, Akinori; Benveniste, Olivier

    2017-10-01

    Sporadic late-onset nemaline myopathy (SLONM) with monoclonal gammopathy of undetermined significance (MGUS) is a rare subacute progressive muscle disease. The prognosis is poor due to severe respiratory insufficiency. Recently, however, autologous stem-cell transplantation following high-dose melphalan has been shown to be effective unless there is delay before the treatment. Therefore, early recognition of the disease is important. This review gives an overview of recent advances in SLONM-MGUS, which could help to understand clinical and pathological features and treatment. Efficacy of autologous stem-cell transplantation following high-dose melphalan has been demonstrated in a long-term observation study. Subsequently, reports from other groups also have supported it. Furthermore, efficacy of chemotherapy toward plasma cell dyscrasia without stem-cell transplantation have been reported as well. A few case reports have suggested the presence of cardiac involvement related to SLONM-MGUS. SLONM-MGUS is now considered as a treatable disease. Antiplasma cell dyscrasia therapy is a promising therapeutic option. Meanwhile, the pathomechanic link between muscle degeneration and monoclonal gammopathy remains unclear and further investigations are warranted.

  2. [Monoclonal gammopathy of undetermined significance and asymptomatic multiple myelom in the year 2014 ].

    Science.gov (United States)

    Adam, Zdeněk; Krejčí, Marta; Pour, Luděk; Sevčíková, Eva; Křivanová, Andrea; Rehák, Zdeněk; Koukalová, Renata; Cermáková, Zdeňka; Vaníček, Jíří; Sevčíková, Sabina

    2014-10-01

    Presence of monoclonal immunoglobulin in serum or urine is a relatively common event affecting about 3.2 % of people over 50. Isolated increase of only one type of free light chain, either κ or λ, is detected in 0.7-0.8 % of people over 50. Most people with monoclonal immunoglobulin meet the criteria of the so-called "mono-clonal gammopathy of undetermined significance (MGUS)". MGUS is defined by concentration of monoclonal immunoglobulin in serum < 30 g/l, number of plasma cells in the bone marrow < 10 % and the absence of symptoms of multiple myeloma and other lymphoproliferative diseases. A proportion of people with MGUS gradually progresses from asymptomatic into symptomatic myeloma or other malignant lymphoproliferative disease requiring treatment. Therefore, MGUS is considered to be one of the most common premalignant conditions with an average risk of transformation into malignant disease of 1 % per year. Monoclonal gammopathy of IgG and IgA subtype can develop into multiple myeloma. Light chain monoclonal gammopathy can develop not only into light chain multiple myeloma but also into AL-amyloidosis and light chain deposition disease (amorphous deposits of light chains damaging organs). IgM monoclonal gammopathy may develop into Waldenstrom macroglobulinemia or other lymphoproliferative disorder, or into rare IgM subtype of multiple myeloma. Unfortunately, people with MGUS are threatened by more than an increased risk of transformation into multiple myeloma or other severe hematologic disease. Pre-malignant clone of plasma cells in the bone marrow causes changes in the bone marrow that directly affect the person. For people with MGUS, there is an increased incidence of osteoporosis and increased fracture risk when compared to the general population. People with MGUS also have an increased risk of bacterial infections and thromboembolic complications compared with the same age population without MGUS. Clonal plasma cells, which are the basis of MGUS, may in

  3. Effect of statins, smoking and obesity on progression of monoclonal gammopathy of undetermined significance: a case-control study.

    Science.gov (United States)

    Thompson, Michael A; Kyle, Robert A; Melton, L Joseph; Plevak, Matthew F; Rajkumar, S Vincent

    2004-05-01

    Interleukin-6 (IL-6) and C-reactive protein (CRP, a surrogate marker for IL-6) are important in monoclonal gammopathy of undetermined significance (MGUS) and myeloma. Smoking and obesity may elevate CRP levels, while statins decrease CRP levels. A case-control study in 200 MGUS patients found that statin use, smoking history and obesity do not affect MGUS progression.

  4. Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

    NARCIS (Netherlands)

    Sathitruangsak, C.; Righolt, C.H.; Klewes, L.; Tammur, P.; Ilus, T.; Tamm, A.; Punab, M.; Olujohungbe, A.; Mai, S.

    2015-01-01

    The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control

  5. Data quality of the monoclonal gammopathy of undetermined significance diagnosis in a hospital registry

    Directory of Open Access Journals (Sweden)

    Gregersen H

    2013-08-01

    Full Text Available Henrik Gregersen,1 Caroline Brenner Larsen,1 Anne Haglund,1 Rikke Mortensen,2 Niels Frost Andersen,3 Mette Nørgaard21Department of Hematology, Aalborg University Hospital, Aalborg, Denmark; 2Department of Clinical Epidemiology, 3Department of Hematology, Aarhus University Hospital, Aarhus, DenmarkObjective: To estimate the positive predictive value (PPV and completeness of the monoclonal gammopathy of undetermined significance (MGUS diagnosis coding in a hospital registry within a population-based health-care setting.Patients and methods: Through the Danish National Patient Registry (DNPR, we identified 627 patients registered with MGUS in two Danish regions during the period January 2001–February 2011. We reviewed the medical records of all patients registered with MGUS at the Department of Hematology, Aalborg University Hospital, and a sample of patients registered at the other three hematological departments in the two regions. We estimated the PPV of the MGUS diagnosis based on this sample of 327 medical records. We also estimated the completeness of the DNPR by linking data from the DNPR and data from a previously validated MGUS cohort of 791 patients identified through the laboratory system covering North Jutland Region.Results: The diagnosis of MGUS was confirmed in 231 patients and assessed as probable in an additional 38 patients, corresponding to a PPV of 82.3% (95% confidence interval [CI] 78.1%–86.4%. By contrast, 58 (17.7% of the patients did not definitively meet the diagnostic criteria for MGUS. When we excluded patients registered with malignant monoclonal gammopathy recorded prior to or within the first year after registration of MGUS in the DNPR, the PPV increased to 88.3% (95% CI 84.5%–92.1%. The DNPR only registered a diagnosis of MGUS in 133 of the 791 MGUS patients identified through the laboratory system, corresponding to a completeness of 16.8% (95% CI 14.1%–19.6%.Conclusion: The PPV of the diagnosis coding for

  6. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance.

    Science.gov (United States)

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-08-28

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density.

  7. Waldenstrom’s Macroglobulinemia and Peripheral Neuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes with a Bleeding Diathesis and Rash

    Directory of Open Access Journals (Sweden)

    S. Haider

    2013-01-01

    Full Text Available We report a case of a 29-year-old male who presented with paraesthesia and skin lesions with excessive bleeding after skin biopsy leading to hematology consultation. He was found to have prolonged partial thromboplastin time (PTT and monoclonal gammopathy on serum protein electrophoresis (SPEP. He experienced excessive bleeding leading to hospitalization after bone marrow biopsy and required blood transfusion. He was diagnosed with Waldenstrom's Macroglobulinemia (WM, based on the presence of IgM-κ type monoclonal (M protein and infiltration of lymphoplasmacytic cells identified in bone marrow aspirates. He was noticed to have features of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome. This is a very rare case of WM with POEMS syndrome which responded to chemotherapy using bortezomib, steroids, and rituximab.

  8. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM): a practical guide to management.

    Science.gov (United States)

    Maciocia, Nicola; Wechalekar, Ashutosh; Yong, Kwee

    2016-11-02

    Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are precursor conditions of symptomatic multiple myeloma (MM). Diagnostic principles are aimed at excluding MM requiring therapy, other conditions associated with paraproteins that may require different management, and risk stratifying patients for the purposes of tailored follow-up and investigation. The International Myeloma Working Group have recently published a revised definition of MM, which singles out a small group of patients with smoldering multiple myeloma who are at very high risk of progression and organ damage; such patients are now included under the definition of MM and recommended to start anti-myeloma treatment. Furthermore, the recently published National Institute of Health and Care Excellence guideline recommends cross-sectional imaging techniques in place of skeletal survey. These recent recommendations are discussed, and practical guidance for investigation and management are presented.

  9. Advances in understanding monoclonal gammopathy of undetermined significance as a precursor of multiple myeloma

    Science.gov (United States)

    Weiss, Brendan M; Kuehl, W Michael

    2010-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) affects at least 3% of the population above the age of 50 and is the precursor to multiple myeloma (MM), an incurable malignancy of plasma cells. Recent advances in MGUS include: an improved understanding of the pathogenesis of MGUS and its progression to MM, involving molecular events intrinsic to the malignant plasma cell as well as the microenvironment; novel techniques to assess risk for progression to MM using serum-free light-chain analysis and immunophenotyping; and a renewed interest in chemoprevention of MM. In the future, continued improvement in our understanding of MGUS will lead to the development of better biomarkers for prognosis and therapies for chemoprevention of MM. PMID:20473362

  10. Discovering the meaning of monoclonal gammopathy of undetermined significance: current knowledge, future challenges.

    Science.gov (United States)

    Palladino, C; Bruno, B; Boccadoro, M

    2014-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a non malignant plasma cell disorder with a relatively low risk of progression to Multiple Myeloma (MM) and to related Plasma cells disordes (lymphoplasmacellular neoplasms, Waldenstrom Macroglobulinemia or light chain amyloidosis). It is a quite common finding, especially in the population above the age of 50 and it can also present in association with many non malignant conditions. Differential diagnosis of symptomatic and asymptomatic forms is the determinant for starting therapy. Over the last few years many advances in the understanding of the biology of MGUS, together with large epidemiological studies, allowed to define risk models to estimate the risk of progression to MM according to MGUS isotype and, more recently, to peculiar flow cytometry findings. The goal of many recent studies aims at evaluating individual patients and their overall risk of progression, the detection of early signs of progression and the development of timely treatment strategies.

  11. Chromosomal aberrations are shared by malignant plasma cells and a small fraction of circulating CD19+ cells in patients with myeloma and monoclonal gammopathy of undetermined significance

    National Research Council Canada - National Science Library

    Zojer, Niklas; Schuster-Kolbe, Judith; Assmann, Irene; Ackermann, Jutta; Strasser, Kathrin; Hubl, Wolfgang; Drach, Johannes; Ludwig, Heinz

    2002-01-01

    In the present study, we aimed to identify distinct structural and numerical chromosomal aberrations in peripheral blood B cells of patients with myeloma and monoclonal gammopathy of undetermined significance (MGUS...

  12. Data quality of the monoclonal gammopathy of undetermined significance diagnosis in a hospital registry

    Science.gov (United States)

    Gregersen, Henrik; Larsen, Caroline Brenner; Haglund, Anne; Mortensen, Rikke; Andersen, Niels Frost; Nørgaard, Mette

    2013-01-01

    Objective To estimate the positive predictive value (PPV) and completeness of the monoclonal gammopathy of undetermined significance (MGUS) diagnosis coding in a hospital registry within a population-based health-care setting. Patients and methods Through the Danish National Patient Registry (DNPR), we identified 627 patients registered with MGUS in two Danish regions during the period January 2001–February 2011. We reviewed the medical records of all patients registered with MGUS at the Department of Hematology, Aalborg University Hospital, and a sample of patients registered at the other three hematological departments in the two regions. We estimated the PPV of the MGUS diagnosis based on this sample of 327 medical records. We also estimated the completeness of the DNPR by linking data from the DNPR and data from a previously validated MGUS cohort of 791 patients identified through the laboratory system covering North Jutland Region. Results The diagnosis of MGUS was confirmed in 231 patients and assessed as probable in an additional 38 patients, corresponding to a PPV of 82.3% (95% confidence interval [CI] 78.1%–86.4%). By contrast, 58 (17.7%) of the patients did not definitively meet the diagnostic criteria for MGUS. When we excluded patients registered with malignant monoclonal gammopathy recorded prior to or within the first year after registration of MGUS in the DNPR, the PPV increased to 88.3% (95% CI 84.5%–92.1%). The DNPR only registered a diagnosis of MGUS in 133 of the 791 MGUS patients identified through the laboratory system, corresponding to a completeness of 16.8% (95% CI 14.1%–19.6%). Conclusion The PPV of the diagnosis coding for MGUS in the DNPR is high and can be further improved by simple data restriction. However, the low completeness raises concern that MGUS patients registered in the hospital system may be highly selected. PMID:24009431

  13. Genomewide profiling of copy-number alteration in monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Mikulasova, Aneta; Smetana, Jan; Wayhelova, Marketa; Janyskova, Helena; Sandecka, Viera; Kufova, Zuzana; Almasi, Martina; Jarkovsky, Jiri; Gregora, Evzen; Kessler, Petr; Wrobel, Marek; Walker, Brian A; Wardell, Christopher P; Morgan, Gareth J; Hajek, Roman; Kuglik, Petr

    2016-12-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy-number alterations (CNAs) in 90 MGUS and 33 MM patients using high-density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10(-5) ) and showed median number of CNAs is lower in MGUS (3, range 0-22) than in MM (13, range 4-38, P = 1.82 × 10(-10) ). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Immunoglobulin m monoclonal gammopathy of undetermined significance and smoldering Waldenström macroglobulinemia.

    Science.gov (United States)

    Kyle, Robert A; Therneau, Terry M; Dispenzieri, Angela; Kumar, Shaji; Benson, Joanne T; Larson, Dirk R; Melton, L Joseph; Rajkumar, S Vincent

    2013-04-01

    Monoclonal gammopathy of undetermined significance of the immunoglobulin M class was diagnosed in 213 patients at the Mayo Clinic, 29 (14%) of whom developed lymphoma, Waldenström macroglobulinemia, or a related disorder over 1567 person-years of follow-up. The cumulative probability of progression was 10% at 5 years, 18% at 10 years, and 24% at 15 years, or approximately 1.5% per year. The concentration of serum monoclonal protein at diagnosis and the initial serum albumin value were the only independent predictors of progression with multivariate analysis. By contrast, during 285 person-years of follow-up, 34 (71%) of 48 patients with smoldering Waldenström macroglobulinemia (SWM) progressed to Waldenström macroglobulinemia (WM), which required therapy, along with amyloid light chain (AL) amyloidosis (1) and lymphoma (1). The cumulative probability of progression was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 65% at 10 years. The percentage of lymphoplasmacytic cells in the bone marrow, size of the serum monoclonal (M) spike, and hemoglobin value were significant independent risk factors for progression.

  15. Should a Study of Monoclonal Gammopathy of Undetermined Significance Be of Clinical Interest to Predict Myeloma Overcome?

    Directory of Open Access Journals (Sweden)

    J Véronique-Baudin

    2016-02-01

    Full Text Available The majority of monoclonal gammopathy of undetermined significance (MGUS are benign forms that require no treatment but can be considered as a pre-cancerous state. Monoclonal gammopathy of undetermined significance is quite frequent, and related to age. The risk of progression to multiple myeloma or another type of malignant lymphoproliferation is estimated at 1% per year. Monoclonal gammopathy of undetermined significance is twice as frequent in patients of African descent, and prevalence is higher for men. Diagnosis of MGUS is made on evidence of a monoclonal component < 30 g/L and no CRAB criteria (hypercalcaemia, renal insufficiency, anaemia, bone lesions. Regular monitoring is required for all MGUS because they can develop into other lymphoproliferative disorders such as multiple myeloma and lymphoma and other haematologic malignancies. In view of the genetic, insular and environmental context specificities of Caribbean populations of African descent, and according to haemophilia trends of the French West Indies cancer registry, it will be interesting to determine incidence and prevalence of MGUS in a country in the Caribbean. No such study has been performed to date. There is a hypothesis for a possible geographic distribution of these blood disorders linked to environmental exposure to pesticides. The expected findings and their potential repercussions will have major public health interest, and should form the basis for a wider prognostic study to determine risk factors for MGUS in the French Caribbean. In a real life exhaustive study, the Martinique Cancer Registry proposes an epidemiological focus on MGUS in Martinique.

  16. Management of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).

    Science.gov (United States)

    Kyle, Robert A; Buadi, Francis; Rajkumar, S Vincent

    2011-06-01

    Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in the white population but is approximately twice that high in the black population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per year, but the risk continues even after more than 25 years of observation. Risk factors for progression include the size of the serum M protein, the type of serum M protein, the number of plasma cells in the bone marrow, and the serum free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM) is characterized by the presence of an M protein level of 3 g/dL or higher and/or 10% or more monoclonal plasma cells in the bone marrow but no evidence of end-organ damage. The overall risk of progression to a malignant condition is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% to 2% per year for the following 10 years. Patients with both MGUS and SMM must be followed up for their lifetime.

  17. [MALT B cell lymphoma with kidney damage and monoclonal gammopathy: a case study and literature review].

    Science.gov (United States)

    Peces, R; Vega-Cabrera, C; Peces, C; Pobes, A; Fresno, M F

    2010-01-01

    We report a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) involving the left kidney and simultaneous onset of a monoclonal gammopathy IgM kappa. No predisposing local inflammatory condition was identified. Following left nephrectomy, the renal specimen showed the centrocyte like cells and lymphoid cells in the lymphoepithelial lesions were positive for CD20 and CD79α. The neoplastic cells expressed monotypic cytoplasmic IgM kappa. The demonstration of bone marrow cells of B-lineage expressing the same monoclonal protein as the tumor suggested bone marrow involvement, even in the absence of identical morphology. Despite chemotherapy and rituximab treatment, clinical follow-up showed right kidney extension with high-grade transformation, and finally systemic dissemination. This case illustrates that the kidney is among the sites that may be involved by MALT B-cell lymphomas in a primary or secondary fashion, and the need for expanded investigation of the possible dissemination. We review the literature on this unusual extranodal lymphoma.

  18. Circulating clonotypic B cells in multiple myeloma and monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Thiago, Leandro S; Perez-Andres, Martin; Balanzategui, Ana; Sarasquete, Maria E; Paiva, Bruno; Jara-Acevedo, Maria; Barcena, Paloma; Sanchez, Maria Luz; Almeida, Julia; González, Marcos; San Miguel, Jesus F; Garcia-Sanz, Ramón; Orfao, Alberto

    2014-01-01

    The B-cell compartment in which multiple myeloma stem cells reside remains unclear. We investigated the potential presence of mature, surface-membrane immunoglobulin-positive B lymphocytes clonally related to the tumor bone marrow plasma cells among different subsets of peripheral blood B cells from ten patients (7 with multiple myeloma and 3 with monoclonal gammopathies of undetermined significance). The presence of clonotypic immunoglobulin heavy chain gene rearrangements was determined in multiple highly-purified fractions of peripheral blood B-lymphocytes including surface-membrane IgM(+) CD27(-) naïve B-lymphocytes, plus surface-membrane IgG(+), IgA(+) and IgM(+) memory CD27(+) B cells, and normal circulating plasma cells, in addition to (mono)clonal plasma cells, by a highly-specific and sensitive allele-specific oligonucleotide polymerase chain reaction directed to the CDR3 sequence of the rearranged IGH gene of tumor plasma cells from individual patients. Our results showed systematic absence of clonotypic rearrangements in all the different B-cell subsets analyzed, including M-component isotype-matched memory B-lymphocytes, at frequencies undetermined significance are usually devoid of clonotypic B cells while the presence of immunophenotypically aberrant myeloma plasma cells in peripheral blood of myeloma patients is a relatively frequent finding.

  19. Management of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM)

    Science.gov (United States)

    KYLE, ROBERT A.; BUADI, FRANC IS; RAJKUMAR, S. VINC ENT

    2014-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in the white population but is approximately twice that high in the black population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per year, but the risk continues even after more than 25 years of observation. Risk factors for progression include the size of the serum M protein, the type of serum M protein, the number of plasma cells in the bone marrow, and the serum free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM) is characterized by the presence of an M protein level of 3 g/dL or higher and/or 10% or more monoclonal plasma cells in the bone marrow but no evidence of end-organ damage. The overall risk of progression to a malignant condition is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% to 2% per year for the following 10 years. Patients with both MGUS and SMM must be followed up for their lifetime. PMID:21888255

  20. Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies.

    Science.gov (United States)

    Tschumper, R C; Dispenzieri, A; Abraham, R S; Henderson, K J; Jelinek, D F

    2013-04-19

    Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.

  1. Cytogenetic profiles in multiple myeloma and monoclonal gammopathy of undetermined significance: a study in highly purified aberrant plasma cells.

    Science.gov (United States)

    Schmidt-Hieber, Martin; Gutiérrez, María Laura; Pérez-Andrés, Martin; Paiva, Bruno; Rasillo, Ana; Tabernero, Maria Dolores; Sayagués, José Maria; Lopez, Antonio; Bárcena, Paloma; Sanchez, María Luz; Gutiérrez, Norma C; San Miguel, Jesus F; Orfao, Alberto

    2013-02-01

    Cytogenetic studies in clonal plasma cell disorders have mainly been done in whole bone marrow or CD138(+) microbead-enriched plasma cells and suggest that recurrent immunoglobulin heavy chain translocations - e.g. t(4;14) -are primary oncogenetic events. The aim of this study was to determine cytogenetic patterns of highly purified aberrant plasma cells (median purity ≥ 98%) in different clonal plasma cell disorders. We analyzed aberrant plasma cells from 208 patients with multiple myeloma (n=148) and monoclonal gammopathy of undetermined significance (n=60) for the presence of del(13q14), del(17p13) and t(14q32) using multicolor interphase fluorescence in situ hybridization. Additionally, immunoglobulin heavy chain gene arrangements were analyzed and complementarity determining region 3 was sequenced in a subset of patients and combined multicolor interphase fluorescence in situ hybridization/immunofluorescent protein staining analyses were performed in selected cases to confirm clonality and cytogenetic findings. At diagnosis, 96% of cases with multiple myeloma versus 77% of monoclonal gammopathy of undetermined significance cases showed at least one cytogenetic alteration and/or hyperdiploidy. The cytogenetic heterogeneity of individual cases reflected coexistence of cytogenetically-defined aberrant plasma cell clones, and led to the assumption that karyotypic alterations were acquired stepwise. Cases of multiple myeloma and monoclonal gammopathy of undetermined significance frequently showed different but related cytogenetic profiles when other cytogenetic alterations such as deletions/gains of the immunoglobulin heavy chain or the fibroblast growth factor receptor 3 were additionally considered. Interestingly, in 24% of multiple myeloma versus 62% of monoclonal gammopathy of undetermined significance patients with an immunoglobulin heavy chain translocation, aberrant plasma cells with and without t(14q32) coexisted in the same patient. Our data suggest that

  2. Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

    OpenAIRE

    Sathitruangsak, C.; Righolt, C.H.; Klewes, L.; Tammur, P.; Ilus, T.; Tamm, A; Punab, M.; Olujohungbe, A; Mai, S.

    2015-01-01

    ABSTRACT The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three‐dimensional structured illumination microscopy (3D‐SIM) increases the spatial r...

  3. Value of serum free light chain testing for the diagnosis and monitoring of monoclonal gammopathies in hematology.

    Science.gov (United States)

    Jagannath, Sundar

    2007-09-01

    The automated quantification of serum free kappa and lambda light chain concentrations provides a highly sensitive tool for the diagnosis and monitoring of monoclonal gammopathies. An abnormal kappa:lambda ratio supports the presence of clonal plasma cell expansion and requires further investigation. More than 94% of myeloma, light chain myeloma, and AL amyloidosis and, likewise, a majority of patients with light chain deposition disease are detectable with this technology. Importantly, these assays identify M-proteins in most patients with oligosecretory disease and permit their recruitment into clinical trials from which they have been previously excluded. Combining serum free light chain testing with traditional electrophoresis provides > 99% accuracy in the first-line diagnosis of monoclonal gammopathies and eliminates the need for urine testing in most instances. One third of patients with monoclonal gammopathy of undetermined significance have an abnormal free light chain ratio, and these patients harbor a greater risk of progression to plasma cell dyscrasia. For monitoring response to therapy, the international uniform response criteria define a normal free light chain ratio as an essential element of the "stringent complete response" category. Because the half-life of free light chains is chain measurements at short sampling intervals allow real-time measurement of treatment-induced tumor kill, and provide prompt indications of chemosensitivity, dose adequacy, need for alternative approaches, and even prognosis, as demonstrated in AL amyloidosis if the involved free light chain concentration normalizes. Clinical applications of these assays will likely increase as their utility is more widely explored.

  4. [Monoclonal gammopathies of undetermined significance do not systematically require a specialized consultation].

    Science.gov (United States)

    Fouquet, G; Amouzou, K; Renaud, L; Carpentier, B; Simonnet, A; Van de Wyngaert, Z; Guidez, S; Demarquette, H; Seynave, M; Deleplanque, D; Yakoub-Agha, I; Facon, T; Leleu, X

    2015-07-01

    Monoclonal gammopathy of undetermined significance (MGUS) is a frequent entity in the general population. The incidence rate of fortuitous discovery of a monoclonal component in asymptomatic patients is increasing nowadays. The majority of MGUS is being addressed to a hematologist for diagnosis or follow-up by their generalist practitioners. The management of MGUS consists of a clinical and biological surveillance as per published and validated international guidelines available for MGUS diagnosis and follow-up. MGUS thus may not necessarily need a specialized consultation and follow-up in a hematology ward, as we believe it could be performed by generalist practitioners. We studied 190 patients addressed to our hematology department of Lille for diagnosis or follow-up of MGUS. Among the patients, 9.5% developed a malignant hemopathy (multiple myeloma or Waldenström macroglobulinemia). Among patients diagnosed with MGUS of IgG isotype and a monoclonal component <15 g/L, 96.2% showed no pejorative outcome: these represent simple and routine prognostic factors that can be assessed at diagnosis in order to predict the risk of progression. Those patients could have easily been followed by their generalist practitioner from the diagnosis of MGUS. A specialist's consultation would still be recommended for patients with pejorative factors at diagnosis, or if a clinical or biological event that could suggest progression occurs during follow-up, or in case of MGUS with complication, in which cases patients would need a specialized management in a hematology department. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  5. Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance.

    Science.gov (United States)

    Crowley, Maeve P; Kevane, Barry; O'Shea, Susan I; Quinn, Shane; Egan, Karl; Gilligan, Oonagh M; Ní Áinle, Fionnuala

    2016-09-01

    The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P < .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies. © The Author(s) 2016.

  6. Immunoparesis and monoclonal gammopathy of undetermined significance are disassociated in advanced age.

    Science.gov (United States)

    Cherry, Benjamin M; Costello, Rene; Zingone, Adriana; Burris, Jason; Korde, Neha; Manasanch, Elisabet; Kwok, Mary; Annunziata, Christina; Roschewski, Mark J; Engels, Eric A; Landgren, Ola

    2013-02-01

    Immunoparesis and a skewed serum free light chain (FLC) ratio are indicators of immune dysfunction predictive of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). Previous studies have reported increased prevalence of MGUS by age, but no study has examined the relationship between immunoparesis and abnormal FLC ratios in the elderly. We screened 453 older adults (median age, 80 years; range, 65-96) to characterize the patterns of immunoparesis and abnormal FLC ratio in relation to MGUS. We defined MGUS in 4.4% of the subjects; the prevalence was 12.5% among individuals of >90 years. In MGUS (vs. non-MGUS) cases, immunoparesis and abnormal FLC ratios were detected in 70.0% (vs. 49.0%; P = 0.07) and 50.0% (vs. 12.9%; P = 0.0001), respectively. Based on small numbers, MGUS patients with abnormal FLC ratio were borderline (P = 0.07) more likely to have immunoparesis. Overall, the prevalence of immunoparesis varied in a nonlinear fashion, with lowest frequencies in the youngest and oldest groups. Our observed disassociation between MGUS prevalence and impaired immunoglobulin production suggests that separate mechanisms are involved in the development of MGUS and immunoparesis in advanced age. These findings emphasize the need for molecularly defined methods to characterize myeloma precursor states and better predict progression to MM. Copyright © 2012 Wiley Periodicals, Inc.

  7. Clinical Comparisons of Two Free Light Chain Assays to Immunofixation Electrophoresis for Detecting Monoclonal Gammopathy

    Directory of Open Access Journals (Sweden)

    Han-Sung Kim

    2014-01-01

    Full Text Available Free light chains (FLCs are useful biomarkers for the diagnosis and monitoring of various plasma cell dyscrasias. One hundred fifty-seven samples from 120 patients for screening or monitoring of monoclonal gammopathy (MG were included. The new N Latex FLC assays (Siemens Healthcare Diagnostics GmbH, Germany were compared with the Freelite FLC assays (The Binding Site Ltd., UK and the results were analyzed with those of immunofixation electrophoresis (IFE. The Freelite FLC assay showed significantly wider assay ranges than the N Latex FLC assay. The correlation coefficients of the two FLC kappa (κ assays, lambda (λ assays, and the κ/λ ratio were 0.9792, 0.8264, and 0.9064, respectively. The concordance rate was 84.7% for the FLC κ assays, 79.6% for FLC λ, and 89.2% for the κ/λ ratio. The clinical sensitivity and specificity of the κ/λ ratios were 72.2% and 93.6% for the Freelite assay and 64.6% and 100% for the N Latex FLC assay. Two FLC assays showed good correlations and concordance. However, the clinical sensitivity of the κ/λ ratio was higher in the Freelite FLC assays; clinical specificity was higher in the N Latex FLC assay. Both FLC assays seem to have limited clinical utility in detecting MG in certain clinical settings.

  8. Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio

    Science.gov (United States)

    Singh, Gurmukh

    2017-01-01

    Background Serum free light chain assay (SFLCA) and κ/λ ratio, and protein electrophoretic methods are used in the diagnosis and monitoring of monoclonal gammopathies. Methods Results for serum free light chains, serum and urine protein electrophoreses and immunofixation electrophoreses in 468 patients with a diagnosis of monoclonal gammopathy were compared. The results of the two methods were graded as concordant, non-concordant or discordant with the established diagnoses to assess the relative performance of the methods. Results of κ/λ ratio in samples with monoclonal protein detectable by electrophoretic methods were also analyzed. Results Protein electrophoreses results were concordant with the established diagnoses significantly more often than κ/λ ratio. The false negative rate for κ/λ ratio was higher than that for electrophoretic methods. κ/λ ratio was falsely negative in about 27% of the 1,860 samples with detectable monoclonal immunoglobulin. The false negative rate was higher in lesions with lambda chains (32%) than those with kappa chains (24%). The false negative rate for κ/λ ratio was over 55% in samples with monoclonal gammopathy of undetermined significance. Even at first encounter, the false negative rates for κ/λ ratios for monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma were 66.98%, 23.08%, and 30.15%, respectively, with false negative rate for lambda chain lesions being higher. Conclusions Electrophoretic studies of serum and urine are superior to SFLCA and κ/λ ratio. Abnormal κ/λ ratio, per se, is not diagnostic of monoclonal gammopathy. A normal κ/λ ratio does not exclude monoclonal gammopathy. False negative rates for lesions with lambda chain are higher than those for lesions with kappa chains. Electrophoretic studies of urine are underutilized. Clinical usefulness and medical necessity of SFLCA and κ/λ ratio is of questionable value in routine clinical testing. PMID:27924175

  9. Prevalence of monoclonal gammopathy of undetermined significance in Asia: a viewpoint from nagasaki atomic bomb survivors.

    Science.gov (United States)

    Iwanaga, Masako; Tomonaga, Masao

    2014-02-01

    Exposure to ionizing radiation is a known environmental risk factor for a variety of cancers including hematological malignancies, such as leukemia, myelodysplastic syndromes, and multiple myeloma. Therefore, for Hiroshima and Nagasaki atomic bomb survivors (surviving victims who were exposed to ionizing radiation emitted from the nuclear weapons), several cancer-screening tests have been provided annually, with government support, to detect the early stage of malignancies. An M-protein screening test has been used to detect multiple myeloma at an early stage among atomic bomb survivors. In the screening process, a number of patients with monoclonal gammopathy of undetermined significance (MGUS), in addition to multiple myeloma, have been identified. In 2009 and 2011, we reported the age- and sex-specific prevalence of MGUS between 1988 and 2004 and the possible role of radiation exposure in the development of MGUS using the screening data of more than 1000 patients with MGUS among approximately 52,000 Nagasaki atomic bomb survivors. The findings included: (1) a significant lower overall prevalence (2.1%) than that observed in Caucasian or African-origin populations; (2) a significantly higher prevalence in men than in women; (3) an age-related increase in the prevalence; (4) a significantly higher prevalence in people exposed to higher radiation doses only among those exposed at age 20 years or younger; and (5) a lower frequency of immunoglobulin M MGUS in Japanese patients than in patients in Western countries. The large study of MGUS among Nagasaki atomic bomb survivors has provided important findings for the etiology of MGUS, including a possible role of radiation exposure on the cause of MGUS and an ethnicity-related difference in the characteristics of MGUS. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Differing coagulation profiles of patients with monoclonal gammopathy of undetermined significance and multiple myeloma.

    Science.gov (United States)

    Crowley, Maeve P; Crowely, Maeve P; Quinn, Shane; Coleman, Eoin; Eustace, Joseph A; Gilligan, Oonagh M; O'Shea, Susan I; Shea, Susan I O

    2015-02-01

    The link between myeloma and thrombosis is well established. Monoclonal gammopathy of undetermined significance (MGUS) has also been associated with an increased risk of thrombosis. It was recently demonstrated that patients with myeloma display changes in thromboelastometry that may indicate a prothrombotic state. There is little data with regard to changes in thromboelastography in patients with myeloma or MGUS. The aim of this study was to investigate the differing coagulation profiles of patients of patients with myeloma and MGUS by means of conventional coagulation tests and thromboelastography. Blood was taken by direct venepuncture from patients with myeloma, MGUS and normal controls. Routine coagulation tests were performed in an accredited hospital laboratory. Thromboelastography (TEG(®)) was performed as per the manufacturer's protocol. Eight patients were recruited in each group. Patients with myeloma had a significantly lower mean haemoglobin level than patients with MGUS or normal controls (p < 0.001). Patients with myeloma had a significantly more prolonged mean prothrombin time than normal controls (p = 0.018) but not patients with MGUS. Patients with myeloma had significantly higher median D-dimer levels than normal controls (p = 0.025), as did patients with MGUS (p = 0.017). Patients with myeloma had a significantly higher mean factor VIII level than normal controls (p = 0.009) and there was a non-significant trend towards patients with MGUS having higher factor VIII levels than normal controls (p = 0.059). There was no significant difference in thromboelastographic parameters between the three groups. Patients with MGUS appear to have a distinct coagulation profile which is intermediate between patients with myeloma and normal controls.

  11. Incidence of Monoclonal Gammopathy of Undetermined Significance and Estimation of Duration Before First Clinical Recognition

    Science.gov (United States)

    Therneau, Terry M.; Kyle, Robert A.; Melton, L. Joseph; Larson, Dirk R.; Benson, Joanne T.; Colby, Colin L.; Dispenzieri, Angela; Kumar, Shaji; Katzmann, Jerry A.; Cerhan, James R.; Rajkumar, S. Vincent

    2012-01-01

    Objectives To determine the incidence of monoclonal gammopathy of undetermined significance (MGUS) in the general population and to estimate the duration of occult MGUS before first diagnosis. Methods To estimate incidence we used innovative methods to exploit the Olmsted County, Minnesota, MGUS prevalence data, along with follow-up from a large cohort of patients with clinically detected MGUS. The prevalence cohort consisted of 21,463 persons systematically screened for the presence or absence of MGUS. The clinical cohort consisted of 7472 patients with MGUS diagnosed at Mayo Clinic from January 1, 1990, to May 13, 2010. The incidence of MGUS was estimated using the prevalence estimates, the rate of MGUS progression, and the death rates from MGUS using Markov chain methods. Results We estimate that the annual incidence of MGUS in men is 120 per 100,000 population at the age of 50 years and increases to 530 per 100,000 population at the age of 90 years. The rates for women are 60 per 100,000 population at the age of 50 years and 370 per 100,000 population at the age of 90 years. We estimate that 56% of women 70 years of age diagnosed as having MGUS have had the condition for more than 10 years, including 28% for more than 20 years. Corresponding values for men are 55% and 31%, respectively. At 60 years of age, the proportion of prevalent cases that are clinically recognized is 13%. This rate increases to 33% at the age of 80 years. Conclusion In addition to an accumulation of cases, the age-related increase in prevalence of MGUS is related to a true increase in incidence with age. When first clinically recognized, MGUS has likely been present in an undetected state for a median duration of more than 10 years. PMID:22883742

  12. [Evaluation of the new Hevylite™ IgA assay for the diagnosis and follow-up of monoclonal gammopathies].

    Science.gov (United States)

    Lakomy, Daniela; Lemaire-Ewing, Stéphanie; Denimal, Damien; Bastie, Jean-Noël; Lafon, Ingrid; Caillot, Denis

    2013-01-01

    Multiple myeloma diagnosis and follow-up are based on monoclonal protein measurement. The estimation of monoclonal immunoglobulin production requires serum protein electrophoresis, immunoelectrophoresis and free light chain assay. However these classical assays have some limitations. Hevylite™ IgA (Binding Site) is a new nephelometric/turbidimetric assay allowing the IgA κ and IgA λ measurement. The aim of this study was to determine the performance of this assay, for the diagnosis and follow-up of myeloma patients at different stages. Sixty seven frozen sera from 26 patients were assayed. Total IgA, IgA κ, IgA λ concentrations, serum protein electrophoresis and serum immunofixation were performed at diagnosis and during follow-up. All myeloma patients had an abnormal IgA κ/IgA λ ratio at diagnosis. During disease monitoring, the IgA κ or IgA λ concentrations correlated well with the electrophoretic estimation of the monoclonal spike and the values of total IgA. Hevylite™ test was more sensitive than serum protein electrophoresis and provided numerical and reproductible assessment of the monoclonal and non-monoclonal isotype. The IgA κ/IgA λ ratio allowed early prediction of disease relapse. Hevylite™ is an interesting assay especially when the monoclonal IgA comigrates on electrophoresis with normal proteins making impossible a reliable densitometric estimation. Hevylite™ might become an important assay in the biological exploration of gammopathies.

  13. Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma.

    Science.gov (United States)

    Wadhera, Rishi K; Kyle, Robert A; Larson, Dirk R; Dispenzieri, Angela; Kumar, Shaji; Lazarus, Hillard M; Rajkumar, S Vincent

    2011-09-15

    During the course of multiple myeloma (MM), new monoclonal proteins of an isotype distinct from the original clone, referred to as secondary monoclonal gammopathy of undetermined significance (MGUS), have been described. We report on the frequency, characteristics, and outcome of secondary MGUS. Of the 1942 patients with MM, 128 (6.6%) developed a secondary MGUS, at a median of 12 months from the diagnosis of MM. The median duration of secondary MGUS was 5.9 months. Secondary MGUS was more common in patients after stem cell transplantation than in those who had not undergone such treatment (22.7% vs 1.6%, P < .001). Overall survival was significantly superior in MM patients who developed secondary MGUS compared with the rest of the cohort (73 vs 38 months, respectively; P < .001). The time of onset and the duration of secondary MGUS, as well as failure to resolve spontaneously, had an effect on overall survival and require further study.

  14. Agent Orange Exposure and Monoclonal Gammopathy of Undetermined Significance: An Operation Ranch Hand Veteran Cohort Study.

    Science.gov (United States)

    Landgren, Ola; Shim, Youn K; Michalek, Joel; Costello, Rene; Burton, Debra; Ketchum, Norma; Calvo, Katherine R; Caporaso, Neil; Raveche, Elizabeth; Middleton, Dan; Marti, Gerald; Vogt, Robert F

    2015-11-01

    Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans. To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans. This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS. Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002. Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs. The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1% (34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk

  15. Upregulation of Dicer is more frequent in monoclonal gammopathies of undetermined significance than in multiple myeloma patients and is associated with longer survival in symptomatic myeloma patients.

    Science.gov (United States)

    Sarasquete, María E; Gutiérrez, Norma C; Misiewicz-Krzeminska, Irena; Paiva, Bruno; Chillón, María C; Alcoceba, Miguel; García-Sanz, Ramón; Hernández, Jesús M; González, Marcos; San-Miguel, Jesús F

    2011-03-01

    Dicer and Drosha are key enzymes in the miRNA-processing pathway which is altered in many human cancers. We analyzed Dicer and Drosha expression levels by quantitative PCR in 151 patients with monoclonal gammopathies: 102 symptomatic myeloma patients, 23 smoldering myelomas and 26 monoclonal gammopathy of undetermined significance. We found that Dicer expression values were significantly higher in monoclonal gammopathy of undetermined significance than in smoldering myelomas and symptomatic myeloma (mean ± SD, 0.84 ± 0.36 vs. 0.60 ± 0.23 and 0.62 ± 0.51; P<0.01). Moreover, the median progression-free survival was significantly longer in symptomatic myeloma patients with high expression of Dicer (not reached vs. 23.6 months; P=0.02). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of monoclonal gammopathies.

  16. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

    NARCIS (Netherlands)

    R. Kyle (Robert); B.G.M. Durie (Brian); S.V. Rajkumar (Vincent); O. Landgren; J. Bladé (Joan); G. Merlini; N. Kröger; H. Einsele (Hermann); D. Vesole (David); M.A. Dimopoulos (Meletios); J.F. San Miguel (Jesús Fernando); H. Avet-Loiseau; R. Hajek (Roman); W. Chen (Wei); K.C. Anderson (Kenneth Carl); H. Ludwig (Heinz); P. Sonneveld (Pieter); S. Pavlovsky; A. Palumbo (Antonio); P.G. Richardson; B. Barlogie (Bart); P. Greipp (Philip); R. Vescio (Robert); I. Turesson; J. Westin (Johan); M. Boccadoro (Mario)

    2010-01-01

    textabstractMonoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is a

  17. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

    NARCIS (Netherlands)

    R. Kyle (Robert); B.G.M. Durie (Brian); S.V. Rajkumar (Vincent); O. Landgren; J. Bladé (Joan); G. Merlini; N. Kröger; H. Einsele (Hermann); D. Vesole (David); M.A. Dimopoulos (Meletios); J.F. San Miguel (Jesús Fernando); H. Avet-Loiseau; R. Hajek (Roman); W. Chen (Wei); K.C. Anderson (Kenneth Carl); H. Ludwig (Heinz); P. Sonneveld (Pieter); S. Pavlovsky; A. Palumbo (Antonio); P.G. Richardson; B. Barlogie (Bart); P. Greipp (Philip); R. Vescio (Robert); I. Turesson; J. Westin (Johan); M. Boccadoro (Mario)

    2010-01-01

    textabstractMonoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is a

  18. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

    NARCIS (Netherlands)

    R. Kyle (Robert); B.G.M. Durie (Brian); S.V. Rajkumar (Vincent); O. Landgren; J. Bladé (Joan); G. Merlini; N. Kröger; H. Einsele (Hermann); D. Vesole (David); M.A. Dimopoulos (Meletios); J.F. San Miguel (Jesús Fernando); H. Avet-Loiseau; R. Hajek (Roman); W. Chen (Wei); K.C. Anderson (Kenneth Carl); H. Ludwig (Heinz); P. Sonneveld (Pieter); S. Pavlovsky; A. Palumbo (Antonio); P.G. Richardson; B. Barlogie (Bart); P. Greipp (Philip); R. Vescio (Robert); I. Turesson; J. Westin (Johan); M. Boccadoro (Mario)

    2010-01-01

    textabstractMonoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is

  19. Influenza vaccination-induced B cell response in monoclonal gammopathy of undetermined significance (MGUS)

    NARCIS (Netherlands)

    Tete, Sarah

    2014-01-01

    Monoklonale gammopathie van onbepaalde betekenis (MGUS) is een proliferatieve plasma cel stoornis die voornamelijk voorkomt onder ouderen. Deze stoornis kan uiteindelijk leiden tot een kwaadaardige vorm van multipel myeloom. Er is sprake van een intrinsiek defect in de productie van immunoglobulines

  20. Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Skrtić, Anita; Korać, Petra; Krišto, Delfa Radić; Ajduković Stojisavljević, Radmila; Ivanković, Davor; Dominis, Mara

    2010-12-01

    Notch signaling is implicated in the pathogenesis of multiple myeloma expressing high level of active Notch proteins NOTCH1 and JAGGED1 in tumor plasma cells. We investigated expression of NOTCH1 and JAGGED1 in bone marrow trephine biopsies of 80 newly diagnosed multiple myeloma and 20 monoclonal gammopathy of undetermined significance patients using immunohistochemical methods. The number of positive tumor cells was counted per 1000 tumor cells and the intensity of staining was assessed semi quantitatively. Multiple myelomas expressed NOTCH1 in 92.31% (72/78) and JAGGED1 in 92.21% (71/77) cases. NOTCH1 staining was strong in the majority of cases (59.7%), whereas JAGGED1 was predominately weak (67.6% of cases). In contrast, both markers were negative in all monoclonal gammopathy of undetermined significance cases. However, upon progression of disease from monoclonal gammopathy of undetermined significance to multiple myeloma (seen in 4 patients), analysis of the subsequent bone marrow biopsy showed weak expression of both markers in tumorous plasma cells. Immunohistochemistry results were compared with the pattern of bone marrow infiltration, plasma cell differentiation, and the presence of t(11;14)(q13,q32), t(14;16)(q32;q23),and t(4;14)(p16.3;q23) and overall survival in multiple myeloma patients. A significant correlation was found between strong NOTCH1 staining in multiple myeloma plasma cells and the diffuse type of bone marrow infiltration (P = .002) and an immature morphologic type of plasma cells (P = .043). After a median follow-up of 20.3 months, in multiple myeloma patients no difference in overall survival between NOTCH1 (P = .484) and JAGGED1 (P = .822) positive and negative cases were found. In conclusion, our results indicate importance of NOTCH1 and JAGGED1 expression in plasma cell neoplasia and a possible diagnostic value of their immunohistochemical evaluation of bone marrow infiltrates for multiple myeloma. Copyright © 2010 Elsevier Inc. All

  1. IgG kappa monoclonal gammopathy of undetermined significance presenting as acquired type III Von Willebrand syndrome.

    Science.gov (United States)

    Howard, Christin R; Lin, Tara L; Cunningham, Mark T; Lipe, Brea C

    2014-09-01

    Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder associated with hematoproliferative disorders, autoimmune conditions, neoplasia and cardiovascular disorders that often present a diagnostic challenge. Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common causes of AVWS that typically presents later in life with mucocutaneous or postsurgical bleeding and multimers consistent with type I or II von Willebrand disease (VWD). Here, we present the case of a patient with a 32-year history of type III VWD that was ultimately found to be AVWS related to an IgG MGUS. In this case report, we highlight the diagnostic challenges of AVWS to ensure proper identification and potentially lifesaving treatment of this rare disorder.

  2. Monoclonal gammopathy of undetermined significance in patients with psoriasis: is it really a side effect of biological therapy?

    Science.gov (United States)

    Conti, Andrea; Esposito, Ilaria; Lasagni, Claudia; Miglietta, Roberta; Padalino, Claudia; Fabiano, Antonella; Pellacani, Giovanni

    2014-11-01

    Moderate-to-severe psoriasis is treated using biological drugs targeting cytokines involved in the pathogenesis of the disease, such as tumor necrosis factor alpha (TNF-α) (adalimumab, infliximab, etanercept) and interleukin 12/23 (IL 12/23) (ustekinumab). There is a slight risk of developing hematological malignancies, such as monoclonal gammopathy of undetermined significance (MGUS) with anti TNF-α agents. There are no data available on anti-IL12/23 drugs. This retrospective study of data from 191 patients describes the appearance and follow-up of MGUS in three patients with psoriasis receiving long-term biological therapy. Since the appearance of MGUS occurred after about 6 years of anti-TNFα treatment in only three subjects, it was deemed unlikely to be due to the biological treatment. The decision not to suspend biological therapy after the appearance of MGUS was taken after careful assessment of the possible risks and benefits. © 2014 Wiley Periodicals, Inc.

  3. Prospective comparison of conventional radiography, low-dose computed tomography and magnetic resonance imaging in monoclonal gammopathies.

    Science.gov (United States)

    Minarik, Jiri; Krhovska, Petra; Hrbek, Jan; Pika, Tomas; Bacovsky, Jaroslav; Herman, Miroslav; Scudla, Vlastimil

    2016-06-01

    We carried out a prospective study in order to identify the best imaging approach for patients with newly diagnosed multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). We assessed the extent of myeloma bone disease (MBD) in 112 individuals - 84 patients with MM and 28 individuals with MGUS. For the detection of osteolytic involvement we used whole-body magnetic resonance imaging (WB-MRI), low-dose computed tomography (LD-CT) and conventional radiography (CR). Each method assessed the presence of osteolytic involvement, compressive fractures and extramedullary involvement in the following regions: skull, spine and chest, pelvis and humerus and femur. We compared the difference in the number and extent of osteolytic involvement, especially the findings in CR negative patients. Conventional radiography showed no superiority in any of the evaluated regions, and failed in the detection of extramedullary massess and spine involvement. WB-MRI was best at imaging the spine including extramedullary involvement, however, detection of osteolytic lesions of the skull was limited in comparison with both CR and LD-CT. Both WB-MRI and LD-CT were comparable in imaging of lesions of pelvis, humerus, femur and the presence of extramedullary masses. LD-CT showed superiority in detection of skull lesions but lower sensitivity in spine compared to WB-MRI. Our results confirm that relying solely on CR in the diagnostics of MM is insufficient. We suggest that the most suitable method for primary assessment of osteolytic involvement in monoclonal gammopathies should include either whole-body MRI together with CR of the skull or, with an equivalent sensitivity, whole body LD-CT.

  4. Hospital population screening reveals overrepresentation of CD5(-) monoclonal B-cell lymphocytosis and monoclonal gammopathy of undetermined significance of IgM type.

    Science.gov (United States)

    Voigtlaender, Minna; Vogler, Birthe; Trepel, Martin; Panse, Jens; Jung, Roman; Bokemeyer, Carsten; Bacher, Ulrike; Binder, Mascha

    2015-09-01

    Monoclonal B-cell lymphocytosis (MBL) and monoclonal gammopathy of undetermined significance (MGUS) result from clonal expansions of mature B or plasma cells. Here, we set out to determine the immunophenotypic/monoclonal immunoglobulin (M protein) features and co-prevalence of MBL and MGUS in a hospital-based cohort of 1909 non-hematooncological patients. Of the evaluable cases, 3.8 % showed evidence for MBL by immunophenotyping, while 9.8 % were screened positive for M protein by immunofixation. With six concomitant cases (0.4 %), MBL and MGUS were not statistically associated. At least in two of these coincident cases, MBL and MGUS were of different clonal origin since both clones had divergent light chain restriction. CD5(-) MBL (57.1 %) and IgM+ MGUS (24.7 %) were strikingly overrepresented compared to population-based screenings and did not progress to overt lymphoma or myeloma during the observation period (mean follow-up of 117 weeks or 110 weeks, respectively). Prevalence and phenotypes suggest that a substantial proportion of incidental MBL and MGUS in hospitalized patients may be attributed to transiently expanded B-cell clones in the context of disease-related immune stimulation rather than reflecting veritable precursors of clonal B-cell malignancies.

  5. Five-Year Follow-up Study of Monoclonal Gammopathy of Undetermined Significance in a Korean Elderly Urban Cohort

    Science.gov (United States)

    Lee, Yun-Gyoo; Bang, Soo-Mee; Lee, Jeong-Ok; Kim, Jin Won; Lee, Keun-Wook; Kim, Jee Hyun; Song, Jung Han; Kim, Tae-Hee; Kim, Ki Woong; Lee, Jong-Seok

    2015-01-01

    Purpose We previously reported the prevalence of monoclonal gammopathy of undetermined significance (MGUS) to be 3.3% among an elderly Korean urban cohort recruited during 2005-2006. Here, we report a 5-year follow-up study of the previously identified MGUS cohort. Materials and Methods The 680 participants from the initial cohort were followed-up for a median of 5 years. Sera were collected between 2010 and 2011. Two-step screening was performed with standard serum electrophoresis followed by immunofixation and determination of the serum concentration of monoclonal-protein (M-protein). Results Of the 680 participants (21 with MGUS), 348 (51%) agreed to participate in the follow-up study and 10 were found to have MGUS. Among the 21 MGUS patients initially identified, nine were followed-up, six had persistent M-protein, and one patient had progressed to multiple myeloma (progression rate, 1.0%/yr). The M-protein disappeared in the remaining two individuals. Among the 339 participants without MGUS who were followed-up, four developed an M-protein. There was no significant difference in survival with respect to the presence of MGUS (p=0.66). Conclusion The 5-year follow-up data show that the natural clinical course of MGUS in Korea is similar to that in Western countries. MGUS was not associated with an increased risk of death over the 5-year study period. PMID:25345461

  6. Immune defects in the risk of infection and response to vaccination in monoclonal gammopathy of undetermined significance and multiple myeloma

    Directory of Open Access Journals (Sweden)

    Sarah eTete

    2014-06-01

    Full Text Available The plasma cell proliferative disorders monoclonal gammopathy of undetermined significance (MGUS and malignant multiple myeloma (MM are characterized by an accumulation of transformed clonal plasma cells in the bone marrow and production of monoclonal immunoglobulin. They typically affect an older population, with median age of diagnosis of approximately 70 years. In both disorders, there is an increased risk of infection due to the immunosuppressive effects of disease and conjointly of therapy in MM, and response to vaccination to counter infection is compromised. The underlying factors in a weakened immune response in MGUS and MM are as yet not fully understood. A confounding factor is the onset of normal aging, which quantitatively and qualitatively hampers humoral immunity to affect response to infection and vaccination. In this review, we examine the status of immune alterations in MGUS and MM and set these against normal aging immune responses. We focus primarily on quantitative and functional aspects of B-cell immunity. Furthermore, we review the current knowledge relating to susceptibility to infectious disease in MGUS and MM, and how efficacy of conventional vaccination is affected by proliferative disease-related and therapy-related factors.

  7. Prognostic Impact of Serum Heavy/Light Chain Pairs in Patients With Monoclonal Gammopathy of Undetermined Significance and Smoldering Myeloma: Long-Term Results From a Single Institution.

    Science.gov (United States)

    Magnano, Laura; Fernández de Larrea, Carlos; Elena, Montserrat; Cibeira, María Teresa; Tovar, Natalia; Aróstegui, Juan I; Pedrosa, Fabiola; Rosiñol, Laura; Filella, Xavier; Yagüe, Jordi; Bladé, Joan

    2016-06-01

    Asymptomatic monoclonal gammopathies, such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), are clinical conditions that usually precede symptomatic multiple myeloma. Therefore, risk stratification is crucial owing to the heterogeneous progression rate among these patients. In previous years, suppression of the uninvolved chain of specific heavy/light chain (HLC) pairs in serum has been identified as a new risk factor in MGUS. The aim of the present study was to investigate the prognostic effect of involved and uninvolved HLC pairs and HLC ratios on progression in a series of patients with MGUS and SMM. All specific serum HLC pairs were measured in 114 patients diagnosed with SMM (n = 27) and MGUS (n = 87) from 1983 to 2003. Also, the HLC ratios were calculated. Progression to symptomatic multiple myeloma was observed in 13 patients (8 with SMM and 5 with MGUS). The risk of progression was 6 times greater in those with SMM (P = .001) and 4 times greater for those with the IgA isotype (P = .01). The suppression of any IgM isotypes (IgMκ or IgMλ) in patients with IgA or IgG gammopathy or any IgA isotypes (IgAκ or IgAλ) in patients with IgG or IgM gammopathy was associated with a shorter time to progression to symptomatic gammopathy (P = .001 and P = .03, respectively). On multivariate analysis, the evolving pattern and suppression of any IgM HLC pair remained significant. HLC ratios could be a valuable tool in the risk stratification of patients with SMM and MGUS, especially patients with IgG isotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study.

    Science.gov (United States)

    Kristinsson, Sigurdur Y; Björkholm, Magnus; Andersson, Therese M-L; Eloranta, Sandra; Dickman, Paul W; Goldin, Lynn R; Blimark, Cecilie; Mellqvist, Ulf-Henrik; Wahlin, Anders; Turesson, Ingemar; Landgren, Ola

    2009-12-01

    There are limited data on survival patterns among patients with monoclonal gammopathy of undetermined significance. We compared the survival of 4,259 patients with monoclonal gammopathy of undetermined significance, collected from hematology outpatient units in Sweden, with the survival of the general population by computing relative survival ratios. We also compared causes of death in these patients with those in 16,151 matched controls. One-, 5-, 10-, and 15-year relative survival ratios were 0.98 (95% CI 0.97-0.99), 0.93 (0.91-0.95), 0.82 (0.79-0.84), and 0.70 (0.64-0.76), respectively. Younger age at diagnosis of the gammopathy was associated with a significantly lower excess mortality compared to that in older patients (pundetermined significance had an increased risk of dying from multiple myeloma (hazards ratio (HR)=553; 95% CI 77-3946), Waldenström's macroglobulinemia (HR=infinity), other lymphoproliferative malignancies (6.5; 2.8-15.1), other hematologic malignancies (22.9; 8.9-58.7), amyloidosis (HR=infinity), bacterial infections (3.4; 1.7-6.7), ischemic heart disease (1.3; 1.1-1.4), other heart disorders (1.5; 1.2-1.8), other hematologic conditions (6.9; 2.7-18), liver (2.1; 1.1-4.2), and renal diseases (3.2; 2.0-4.9). Our finding of decreased life expectancy in patients with monoclonal gammopathy of undetermined significance, which was most pronounced in the elderly and explained by both malignant transformation and non-malignant causes, is of importance in the understanding and clinical management of this disease. The underlying mechanisms may be causally related to the gammopathy, but may also be explained by underlying disease that led to the detection of the hematologic disease. Our results are of importance since they give a true estimation of survival in patients with monoclonal gammopathy of undetermined significance diagnosed in clinical practice.

  9. [Secondary monoclonal gammopathy after bone marrow autotransplantation as a cause of worse renal function in light chain immunoglobulin deposition disease].

    Science.gov (United States)

    Rekhtina, I G; Mendeleeva, L P; Stolyarevich, E S; Galtseva, I V; Povilaitite, P E; Biryukova, L S

    2016-01-01

    The paper describes a clinical case of a female woman with nephropathy due to light chain deposition disease caused by secretion of κ Bence-Jones protein. Complete immunochemical remission was achieved after induction therapy using a bortezomib + cyclophosphamide + dexamethasone regimen. Renal function remained unchanged (glomerular filtration rate 16 ml/min), there was a reduction in proteinuria from 5.8 to 2.6 g/day. High-dose melphalan (200 mg/m2) chemotherapy with peripheral blood stem cell autotransplantation was performed as consolidation of remission. A year posttransplantation, there was no secretion of κ light chains; however, monoclonal IgG lambda emerged in a quantity of 3.2 g/l. At the same period, nephrotic syndrome became progressive (daily proteinuria 12 g) and dialysis-dependent renal failure developed. A repeat renal biopsy specimen revealed changes, suggesting that there was a decrease in renal deposits of κ light chains. Simultaneously with this, the obvious negative trend as progressive nephrosclerosis and fixation of IgG and λ light chains in the glomeruli (in the sclerotic areas) cause IgGλ monoclonal protein to be involved in the genesis of further kidney injury. Attention is also paid to different characteristics of capillary wall deposits by density (according to the electron microscopic findings), which may point to their different qualitative composition and possibly different formation duration. Papaprotein Gλ disappeared after a year without therapy, suggesting its reactivity. The findings confirm that worse renal function is caused by the action of paraprotein Gλ due to secondary (after autologous hematopoietic stem cells transplantation) monoclonal gammopathy.

  10. Lymphocyte profiles in multiple myeloma and monoclonal gammopathy of undetermined significance: flow-cytometric characterization and analysis in a two-dimensional correlation biplot.

    Science.gov (United States)

    Van den Hove, L E; Meeus, P; Derom, A; Demuynck, H; Verhoef, G E; Vandenberghe, P; Boogaerts, M A

    1998-06-01

    The distribution of 27 T-, B-, and natural killer-cell subsets in the peripheral blood of 40 patients with multiple myeloma (MM), ten patients with monoclonal gammopathy of undetermined significance (MGUS), and 40 healthy donors was investigated by means of classical univariate statistics and advanced multivariate data-analytical techniques. The latter approach was used to describe, represent, and analyze lymphocyte subset distribution in a two-dimensional correlation biplot, allowing comparison of complex lymphocyte profiles (i.e., compound lymphocyte subset distributions) of individual subjects rather than isolated subset values of selected patient and/or donor groups. The correlation biplot revealed that, in accordance with the univariate statistics, the MM patients were characterized by marked shifts towards CD8+, CD57+, CD62L-, CD(16+56)+, and HLA-DR+ T cells, suggesting in vivo immune activation. The activation profile was most markedly observed in treated MM patients in the advanced disease stage category. The lymphocyte profiles of MGUS patients were heterogeneous, with approximately half of them located in the swarm of MM patients and the other half in the swarm of healthy donors. Although the univariate statistics revealed significant differences between MGUS patients and healthy donors only within the B-cell compartment, the correlation biplot revealed that two MGUS patients clearly had a typical T-cell activation profile similar to that of the MM patients. One MGUS patient with a T-cell activation profile progressed 13 months later to a stage IA MM and required chemotherapy. A marked lymphocyte profile shift in one MM patient was associated with terminal and aggressive disease transformation. Our study illustrates further the practical use of correlation biplots for the detection of aberrant lymphocyte profiles and/or profile shifts in individual patients.

  11. Immunoglobulin heavy chain/light chain pairs (HLC, Hevylite™) assays for diagnosing and monitoring monoclonal gammopathies.

    Science.gov (United States)

    Kraj, Maria

    2014-01-01

    Immunofixation (IFE) is a standard method for detecting monoclonal immunoglobulins and characterizing its isotype. Recently clonality can also be determined by using immunoglobulin (Ig) heavy chain/light chain immunoassays - HLC, HevyliteTM. HLC separately measures in pairs light chain types of each intact Ig class generating ratios of monoclonal Ig/uninvolved polyclonal Ig concentrations. Studies have shown that HLC and IFE are complementary methods. HLC assays quantify monoclonal proteins and identify monoclonality. It is possible to predict prognosis in multiple myeloma and to monitor response to treatment using HLC ratio. HLC ratio may serve as a parameter for myeloma induced immunoparesis and serve as a new marker for validating remission depth and relapse probabilities.

  12. Gamopatias monoclonais: critérios diagnósticos e diagnósticos diferenciais Monoclonal gammopathies: diagnosis criteria and differential diagnosis

    Directory of Open Access Journals (Sweden)

    Rosa Malena D. Faria

    2007-03-01

    Full Text Available As gamopatias monoclonais constituem um grupo de desordens caracterizado pela proliferação monoclonal de plasmócitos, que produzem e secretam imunoglobulina ou fragmento de imunoglobulina monoclonal (proteína M . Este artigo propõe uma revisão dos critérios diagnósticos das principais gamopatias monoclonais e diagnósticos diferenciais, uma vez que é comum a sobreposição de muitas características clínicas entre suas variantes. A gamopatia monoclonal de significado indeterminado (MGUS é definida pela presença de proteína M sérica 30% ou plasmocitoma documentado por biópsia. Se a lesão óssea decorre de plasmocitoma solitário ou somente osteoporose, sem fratura, a plasmocitose medular também precisa ser > 30%, para preencher critérios de MM. As gamopatias monoclonais podem estar associadas a diversas doenças, incluindo desordens linfoproliferativas, reumatológicas, neurológicas, dermatológicas e infecciosas. A definição das características clínicas e laboratoriais de cada entidade, maligna ou benigna, facilita o diagnóstico das gamopatias monoclonais e, como conseqüência, seu manejo clínico pelos médicos assistentes.Monoclonal gammopathies are a group of disorders characterized by proliferation of monoclonal plasma cells, which produce and secrete monoclonal immunoglobulin or fragments of monoclonal immunoglobulin (M protein. This paper proposes to review diagnostic criteria of the most important monoclonal gammopathies and their differential diagnosis, because superposition of many clinical characteristics is common between variants. The monoclonal gammopathy of undetermined significance (MGUS is defined by the presence of serum M protein < 3g/dL and/or urinary M protein < 1g/24h, bone marrow plasma cell < 10%, and absence of organ and tissue damage. Asymptomatic multiple myeloma (MM is characterized by the presence of M protein, bone marrow or tissue biopsy plasma cell infiltration, and non-compliance of the

  13. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies.

    Science.gov (United States)

    Korde, Neha; Kristinsson, Sigurdur Y; Landgren, Ola

    2011-05-26

    Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

  14. The Hematologic Definition of Monoclonal Gammopathy of Undetermined Significance in Relation to Paraproteinemic Keratopathy (An American Ophthalmological Society Thesis).

    Science.gov (United States)

    Lisch, Walter; Wasielica-Poslednik, Joanna; Kivelä, Tero; Schlötzer-Schrehardt, Ursula; Rohrbach, Jens M; Sekundo, Walter; Pleyer, Uwe; Lisch, Christina; Desuki, Alexander; Rossmann, Heidi; Weiss, Jayne S

    2016-08-01

    To determine if paraproteinemic keratopathy (PPK) in the setting of monoclonal gammopathy of undetermined significance (MGUS) causes distinct patterns of corneal opacification that can be distinguished from hereditary, immunologic, or inflammatory causes. A retrospective, interventional study of patients showed distinct bilateral opacity patterns of the cornea at the eye clinics of Hanau, Mainz, Helsinki, Marburg, and Berlin between 1993 and 2015. Data on patient characteristics and clinical features on ophthalmic examination were collected, and serum protein profiles were evaluated. A literature review and analysis of all published studies of MGUS with PPK is also presented. The largest group of patients diagnosed with MGUS-induced PPK is analyzed in this study. We studied 22 eyes of 11 patients (6 male, aged 43 to 65, mean age 54; 5 female, aged 49 to 76, mean age 61) with distinct corneal opacities and visual impairment who were first suspected of having hereditary, inflammatory, or immunologic corneal entities. Subsequently, serum protein electrophoresis revealed MGUS to be the cause of the PPK. Literature review revealed 72 patients with bilateral PPK (34 male, mean age 57; 38 female, mean age 58) in 51 studies of MGUS published from 1934 to 2015 and disclosed six additional corneal opacity patterns. This thesis shows that MGUS is not always an asymptomatic disorder, in contrast to the hematologic definition, which has no hint of PPK. The MGUS-induced PPK can mimic many other diseases of the anterior layer of the eye. A new clinical classification for PPK in MGUS is proposed.

  15. Quantitative superresolution microscopy reveals differences in nuclear DNA organization of multiple myeloma and monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Sathitruangsak, Chirawadee; Righolt, Christiaan H; Klewes, Ludger; Tammur, Pille; Ilus, Tiiu; Tamm, Anu; Punab, Mari; Olujohungbe, Adebayo; Mai, Sabine

    2015-05-01

    The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM. © 2014 Wiley Periodicals, Inc.

  16. [Systemic Buschke's scleredema with cardiomyopathy, monoclonal IgG kappa gammopathy and amyloidosis. Case report with autopsy].

    Science.gov (United States)

    Paz, R A; Badra, R E; Martí, H M; Maxit, M J

    1998-01-01

    A 73 year old retired truck driver and blacksmith was studied in June 1996 for thoracic pain and was diagnosed as acute pericarditis which responded well to steroid treatment. In January 1997, he noted swelling of the abdominal skin, genitalia and limbs, sparing the feet. He was euthyroid, did not have evidence of diabetes or a Raynaud's phenomenon. His proteinogram showed an IgG-Kappa monoclonal paraprotein M component, 1.31 g/oo. TSH and tetraiodotironine were normal; ESR 16 mm in the first hour. As he did not respond to treatment he was referred to our hospital in March 1997. On physical examination the most relevant findings were a non-pitting edema of the abdomen and lower limbs, sparing the feet. An echocardiogram was consistent with an infiltrative cardiomyopathy. Soon after his hospitalization his condition worsened suddenly with severe bradicardia (28/minute) due to a junctional rhythm and righ bundle branch block. He suffered a cardiac arrest and died. The autopsy findings favoured the diagnosis of systemic scleredema adultorum of Buschke. Amyloid deposits were also found although not abundant, with a similar distribution except in the skin. In this article the clinical and autopsy findings are presented in a patient showing coexistence of systemic Buschke's scleredema with an infiltrative cardiomyopathy, IgG Kappa gammopathy and amyloidosis.

  17. The value of serum immunoglobulin free light chain assessment in patients with monoclonal gammopathies and acute renal failure.

    Science.gov (United States)

    Cirit, Mustafa; Uzüm, Atilla; Ozen, Pınar; Sentürk, Banu A; Bozkaya, Giray; Payzin, Bahriye; Ural, Orçun

    2012-12-01

    Immunoglobulin free light chain (FLC) abnormalities are common in patients with monoclonal gammopathies and the kidneys are the most affected organs. Immunoassays that provide quantitative measurement of FLC in serum indicate monoclonal FLC production based on the presence of an abnormal FLC kappa:lambda (κ:λ) ratio. The aim of this study was to assess the utility of serum FLC measurement as a diagnostic tool for detecting plasma cell dyscrasias in comparison to standard assays, and to ascertain its sensitivity and specificity in patients with acute renal failure (ARF). Sera from 82 patients with ARF were assessed using serum protein electrophoresis (SPE), serum immunofixation electrophoresis (SIFE), and FLC measurement. The sensitivity and specificity of the FLC ratio in identifying which ARF patients had multiple myeloma (MM) was compared to those of SPE and SIFE. Among the 82 patients with ARF, 7 were diagnosed as MM using SPE, SIFE, and bone marrow biopsy techniques. In total, 8 patients did not have a FLC κ:λ ratio that was within the published reference range (0:26-1:65); the FLC κ:λ ratio based on FLC measurement had a specificity of 96% and sensitivity of 71%, and positive and negative predictive values of 62.9% and 97.3%, respectively, for the diagnosis of MM. The sensitivity and specificity of the FLC κ:λ ratio for diagnosing MM in patients that presented with ARF were lower than those of SPE and SIFE. To further delineate the utility of the FLC κ:λ ratio additional prospective, well-designed large-scale studies are needed. None declared.

  18. A sporadic case of late-onset familial amyloid polyneuropathy with a monoclonal gammopathy.

    Science.gov (United States)

    Correia, Ana Sofia; Mendonça, Marcelo; Caetano, André; Medeiros, Elmira

    2015-08-01

    A 77-year-old Portuguese woman reported gradual worsening of burning and numbness in the feet and hands, fatigue, anorexia, weight loss, diarrhoea and decreased visual acuity. She had a medical history of atrial fibrillation and recent episodes of dizziness and blood pressure fluctuations. There was no relevant family history. The diagnostic workup documented a severe axonal sensorimotor peripheral neuropathy, a monoclonal IgG kappa protein on serum, a severe left ventricular hypertrophy on the echocardiogram and probable vitreous deposits of amyloid on ophthalmologic examination. Pain and dysautonomia with an axonal neuropathy and multisystemic involvement raised the possibility of amyloidosis. The presence of a detectable monoclonal protein, older age at disease onset and absence of family history of disease usually suggest immunoglobulin light-chain amyloidosis. However, in this case, both the genetic testing and the biopsy of the salivary glands confirmed transthyretin amyloidosis. In those patients with a monoclonal protein, particularly in sporadic and late-onset cases, the diagnosis of transthyretin amyloidosis can be challenging, mimicking immunoglobulin light-chain amyloidosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Neoplastic and non-neoplastic complications of solid organ transplantation in patients with preexisting monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Goebel, Teresa E; Schiltz, Nicholas K; Woodside, Kenneth J; Pillai, Aiswarya Chandran; Caimi, Paolo F; Lazarus, Hillard M; Koroukian, Siran M; Campagnaro, Erica L

    2015-09-01

    Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3-7% of the elderly population, with higher prevalence in renal failure patients, and is associated with a 25-fold increased lifetime risk for plasma cell myeloma (PCM), also known as multiple myeloma. Using the California State Inpatient, Emergency Department, and Ambulatory Surgery Databases components of the Healthcare Cost and Utilization Project (HCUP), we sought to determine whether patients with MGUS who undergo solid organ allograft (n = 22,062) are at increased adjusted relative risk (aRR) for hematologic malignancy and other complications. Among solid organ transplant patients, patients with preexisting MGUS had higher aRR of PCM (aRR 19.46; 95% CI 7.05, 53.73; p < 0.001), venous thromboembolic events (aRR 1.66; 95% CI 1.15, 2.41; p = 0.007), and infection (aRR 1.24; 95% CI 1.06, 1.45; p = 0.007). However, when comparing MGUS patients with and without solid organ transplant, there was decreased aRR for PCM with transplant (aRR 0.34; 95% CI 0.13, 0.88; p = 0.027), and increased venous thromboembolic events (aRR 2.33; 95% CI 1.58, 3.44; p < 0.001) and infectious risks (aRR 1.44; 95% CI 1.23, 1.70; p < 0.001). While MGUS increased the risk of PCM overall following solid organ transplantation, there was lower risk of PCM development compared to MGUS patients who did not receive a transplant. MGUS should not preclude solid organ transplant. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Somatic mutation spectrum in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape compared to multiple myeloma.

    Science.gov (United States)

    Mikulasova, Aneta; Wardell, Christopher P; Murison, Alexander; Boyle, Eileen M; Jackson, Graham H; Smetana, Jan; Kufova, Zuzana; Pour, Ludek; Sandecka, Viera; Almasi, Martina; Vsianska, Pavla; Gregora, Evzen; Kuglik, Petr; Hajek, Roman; Davies, Faith E; Morgan, Gareth J; Walker, Brian A

    2017-05-26

    Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma with a 1% risk of progression per year. Although targeted analyses have shown the presence of specific genetic abnormalities such as IGH translocations, RB1 deletion, 1q gain, hyperdiploidy or RAS genes mutations, little is known about the molecular mechanism of malignant transformation. We have performed whole exome sequencing together with CGH+SNP array analysis in 33 flow-cytometry separated abnormal plasma cell samples from MGUS patients to describe somatic gene mutations and chromosome changes at the genome-wide level. Non-synonymous mutations and copy-number alterations were present in 97.0% and in 60.6% of cases, respectively. Importantly, the number of somatic mutations was significantly lower in MGUS compared to myeloma (P < 10-4) and we identified six genes that were significantly mutated in myeloma (KRAS, NRAS, DIS3, HIST1H1E, EGR1 and LTB) within the MGUS dataset. We also found a positive correlation with increasing chromosome changes and somatic gene mutations. IGH translocations were present in 27.3% of cases comprising t(4;14), t(11;14), t(14;16) or t(14;20) and were present in a similar frequency to myeloma, consistent with the primary lesion hypothesis. MYC translocations and TP53 deletions or mutations were not detected in MGUS samples indicating they may be drivers of progression to myeloma. Data from this study show that MGUS is genetically similar to myeloma, however overall genetic abnormalities are present at significantly lower levels compared to myeloma. Copyright © 2017, Ferrata Storti Foundation.

  1. Analyzing Relationship Between Monoclonal Gammopathy of Undetermined Significance (MGUS) with Different Types of Neuropathy: An Observational Study.

    Science.gov (United States)

    Nabi, Shahzaib; Kahlon, Pushpinderdeep; Bozorgnia, Farshid; Arshad, Adeel; Saleem, Akmam; Kuriakose, Philip

    2016-06-01

    To analyze multiple variables, including immunoglobulin subtypes in patients with monoclonal gammopathy of undetermined significance (MGUS) and different types of neuropathy. This was a retrospective, single center study done in a tertiary care hospital in the United States. The data was collected for years 2001-2011. Inclusion criteria were the presence of MGUS and neuropathy. Exclusion criteria were the presence of other factors such as diabetes, vitamin B12 deficiency, alcoholism etc. which can cause neuropathy. Patients with IgM MGUS were compared with patients having Non-IgM MGUS. A total of 281 patients were analyzed in this study. The average age at the time of diagnosis of MGUS and neuropathy was 68 years. The most common type of neuropathy was sensorimotor peripheral neuropathy (46 %). The most common location of neuropathy was the lower extremities (68 %). Among our patients, 52 % had their neuropathy symptoms for 1-5 years before presenting to the clinic. When IgM MGUS was compared with Non-IgM MGUS, a statistically significant difference was found in terms of race (White vs. Others, OR 4.43, 95 % CI 2.13, 9.19, p < 0.001) and survival status (OR 1.98, 95 % CI 1.01, 3.90, p = 0.046). Patients with MGUS are prone to develop different types of neuropathies. Caucasians are more likely to have IgM MGUS as compared to other races. IgM MGUS is generally related to worse outcomes as compared to Non-IgM MGUS. Medical therapies, including gabapentin and pregabalin are effective treatments and the response rate can be as high as 80-90 % with these medications.

  2. Interphase fluorescence in situ hybridization in multiple myeloma and monoclonal gammopathy of undetermined significance without and with positive plasma cell identification

    DEFF Research Database (Denmark)

    Christensen, Jacob H; Abildgaard, Niels; Plesner, Torben

    2007-01-01

    Interphase fluorescence in-situ hybridization (i-FISH) was used to investigate 192 patients with multiple myeloma (MM; n = 182) and benign monoclonal gammopathy of undetermined significance (MGUS; n = 10). Of the 182 MM cases, 132 were investigated without and 50 with positive plasma cell......32. Of these, translocations t(4;14) constituted 9% and t(11;14), 20%. Finally, based on the small number of cytogenetically abnormal cases, it is recommended to include cytogenetics (and, for example, the DNA index) in the prognostic armamentarium....

  3. The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma.

    Science.gov (United States)

    Sigurdardottir, Elin Edda; Turesson, Ingemar; Lund, Sigrun Helga; Lindqvist, Ebba K; Mailankody, Sham; Korde, Neha; Björkholm, Magnus; Landgren, Ola; Kristinsson, Sigurdur Y

    2015-05-01

    Multiple myeloma (MM) is consistently preceded by the precursor state, monoclonal gammopathy of undetermined significance (MGUS). The average annual risk of progression from MGUS to multiple myeloma is 0.5% to 1.0%. Current guidelines suggest life-long clinical follow-up of individuals diagnosed as having MGUS depending on risk stratification. The impact of diagnosing and conducting clinical follow-up of MGUS on MM survival is unclear. To estimate the impact of prior knowledge of MGUS diagnosis and comorbidities on MM survival. We conducted a population-based study including all patients with MM (MM patients) diagnosed in Sweden (n = 14,798) from 1976 to 2005 (with follow-up until 2007); 394 (2.7%) had previously been diagnosed as having MGUS. Information on comorbidities was gathered for all patients. We calculated survival rates from the time of MM diagnosis, comparing patients with vs those without prior knowledge of MGUS. Using Cox proportional hazards models, we calculated hazard ratios (HRs) and 95% CIs for risk factors for death. χ2 Tests were used to evaluate differences in comorbidities. Prior knowledge of MGUS among MM patients. In a subanalysis, monoclonal (M)-protein concentration and type were used as exposure. Risk of death and comorbidities. Patients with MM with prior knowledge of MGUS had significantly (HR, 0.86; 95% CI, 0.77-0.96; P < .01) better overall survival (median survival, 2.8 years) than MM patients without prior knowledge of MGUS (median survival, 2.1 years), although MM patients with (vs without) prior knowledge of MGUS had more comorbidities (P < .001). Among MM patients with prior knowledge of MGUS, low M-protein concentration (<0.5 g/dL) at MGUS diagnosis was associated with poorer MM survival (HR, 1.86; 95% CI, 1.13-3.04; P = .01). Patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. The observation that a low M-protein concentration

  4. [Analysis of serum levels of Dickkopf-1 (DKK-1) in monoclonal gammopathy of undetermined significance and multiple myeloma].

    Science.gov (United States)

    Ščudla, Vlastimil; Petrová, Pavla; Pika, Tomáš; Lochman, Pavel; Minařík, Jiří; Bačovský, Jaroslav; Srovnalík, Karel

    2015-01-01

    Several recent studies aim at the detection of biological parameters that enable more precise diagnostics and stratification of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). The objective of our study was to assess the potential contribution of serum levels of Dickkopf-1 (DKK-1) in MGUS and MM from the point of more specific differentiation of both conditions, and the relationship of DKK-1 to selected laboratory parameters, individual forms and clinical stages of both conditions. The analyzed cohort consisted of 46 individuals with MGUS and 152 patients with MM at the time of diagnosis. For the assessment of serum levels of DKK-1 we used ELISA method. We assessed also serum levels of free light chains (FLC) κ and λ using the Freelite system, and β2-microglobulin (β2-M) using the Immulite 1000 method. For statistical estimation we used: Pearson χ2-test, U-test according to Mann-Whitney and Kruskal-Wallis test. Our analysis revealed that there was no significant difference between the levels of DKK-1 in MGUS risk groups (0-3) and between the states with different FLC concentration including the κ/λ index of monoclonality. In MM there was a significant relationship of DKK-1 to the level of hemoglobin (p<0.008) but not to the levels of FLC, creatinine or β2-microglobulin. Within the Durie-Salmon staging system, there were significant differences of DKK-1 between the stages I vs. III (p=0.001) and I vs. II+III (p=0.002). In the International Staging System (ISS) there were significant differences only between stages 1 vs. 2+3 (p=0.045). Although there was no overall significant difference of DKK-1 levels between MGUS and MM, there was a difference between MGUS vs stage III (p=0.001) and II+III (p=0.001) according to Durie-Salmon, and also MGUS vs. stage 2 (p=0.005) and vs. stages 2+3 (p=0,012) according to ISS. There were no significant differences in DKK-1 between MGUS and initial/asymptomatic form of MM (stage I

  5. Transplante de células-tronco hematopoéticas em gamopatias monoclonais Hematopoietic stem cell transplantation for monoclonal gammopathies

    Directory of Open Access Journals (Sweden)

    Angelo Maiolino

    2010-05-01

    Full Text Available O transplante de células-tronco hematopoéticas (TCTH é um procedimento de fundamental importância na estratégia terapêutica das gamopatias monoclonais. No mieloma múltiplo, em particular, o TCTH autólogo está indicado como estratégia de primeira linha para pacientes até 70 anos de idade. Nesta capítulo serão discutidas as indicações, estratégias e recomendações envolvendo o TCTH em gamopatias monoclonais, amiloidose e POEMS, frutos da Reunião de Consenso da Sociedade Brasileira de Transplante de Medula Óssea.Hematopoietic stem cell transplantation (HSCT is an important strategy in the treatment of monoclonal gammopathies. For multiple myeloma, in particular, autologous HSCT is indicated as first line therapy for under 70-year-old patients. In this chapter we will discuss indications, strategies and recommendations involving HSCT for monoclonal gammopathies from the Consensus Meeting of the Brazilian Society of Bone Marrow Transplantation.

  6. Research progress in monoclonal gammopathy of undetermined significance%意义未明单克隆免疫球蛋白血症研究进展

    Institute of Scientific and Technical Information of China (English)

    江滨; 刘念

    2008-01-01

    意义未明单克隆免疫球蛋白血症(monoclonal gammopathy of undetermined significance,MGUS)指血清中出现单克隆免疫球蛋白,但缺乏浆细胞病或其他相关疾病,如Waldenstroms巨球蛋白血症(WM)、原发性淀粉样变(AL)、B细胞淋巴瘤(B—NHL)、慢性白血病(CLL)的证据和特征。曾一度被称作为“良性单克隆免疫球蛋白病(benign monoclonal gammopathy,BMG)”,

  7. Ocular copper deposition associated with monoclonal gammopathy of undetermined significance: case report Depósito ocular de cobre associado a gamopatia monoclonal de significância indeterminada: relato de caso

    Directory of Open Access Journals (Sweden)

    Patrick F. Tzelikis

    2005-08-01

    Full Text Available To report a case of ocular copper deposition in both eyes at the level of Descemet's membrane associated with a monoclonal gammopathy of undetermined significance (MGUS. A 49-year-old white woman had golden-brown metallic dust-like deposits on Descemet's membrane of both eyes. A systemic examination revealed an elevated serum copper, normal serum ceruloplasmin and a normal level of total protein. Serum protein electrophoresis demonstrated a single peak (M-spike in the gamma region (M-protein in serum = 11 g/l. Flow cytometric analysis of the marrow aspirate identified a monoclonal plasma cell population that represents approximately 2% of the total marrow cells consistent with the diagnosis of monoclonal gammopathy of undetermined significance. Copper deposits at the level of Descemet's membrane may be a finding in a patient with monoclonal gammopathy of undetermined significance.Relatar um caso de depósito corneano de cobre em ambos os olhos a nível da membrana de Descemet associado a gamopatia monoclonal de significância indeterminada (GMSI. Paciente feminina, 49 anos, leucodérmica, apresentando depósito corneano de aspecto marrom-ouro a nível da membrana de Descemet em ambos os olhos. Exame sistêmico revelou cobre sérico elevado, ceruloplasmina sérica normal, e proteína total normal. Eletroforese de proteínas séricas demonstrou um pico único na região gama (proteína M = 11 g/l. Análise citométrica de aspirado medular evidenciou uma população de células plasmáticas monoclonais de aproximadamente 2% do total de células medulares consistente com o diagnóstico de gamopatia monoclonal de significância indeterminada. Depósitos de cobre a nível da membrana de Descemet podem ser encontrados em pacientes com gamopatia monoclonal de significância indeterminada.

  8. Autoimmunity related to IgM monoclonal gammopathy of undetermined significance. Peripheral neuropathy and connective tissue sensibilization caused by IgM M-proteins

    DEFF Research Database (Denmark)

    Jønsson, V; Schrøder, H D; Nolsøe, C

    1988-01-01

    against structures in the endoneurium but no IgM autoimmunity in the direct fluorescence test. The latter improved clinically in parallel with a decrease in the M-protein indicating a pathogenetic role of the autoantibody. In three other cases, the IgM was bound to connective tissue structures, two......In eight of 10 consecutive cases of IgM monoclonal gammopathy of undetermined significance (MGUS), the M-protein had specificity towards various tissues as estimated by direct and indirect immunofluorescence studies of skin and/or sural nerve biopsies. Five of the cases had neuropathy. In three...... of them also had plasma antibodies against the peri- and endoneurium in the indirect fluorescence test. Finally, two cases showed no reaction of the M-protein against any tissue structures. Since an autoimmune pathogenesis is suspected, the HLA types of seven patients are reported....

  9. Monoclonal Gammopathy of Undetermined Significance with Amyloid Deposition in the Lung and Non-Amyloid Eosinophilic Deposition in the Brain: A Case Report

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    Francois Abi-Fadel

    2010-01-01

    Full Text Available Background. Monoclonal gammopathy of undetermined significance (MGUS is rarely complicated by amyloidosis. Case. A 66-year-old white male presented to the emergency room (ER after an unwitnessed fall and change in mental status. Patient was awake and alert but not oriented. There was no focal deficit on neurological exam. Past medical history (PMH included hypertension, hypercholesterolemia, aortic valve replacement (nonmetallic, incomplete heart block controlled by a pacemaker and IgG- IgA type Monoclonal Gammopathy of Undetermined Significance. The MGUS was diagnosed 9 months ago on serum protein electrophoresis (SPEP as patient was referred to the outpatient clinic for hyperglobulinemia on routine blood work. In ER, a head-computed tomography (CT revealed multiple parenchymal hemorrhagic lesions suspicious for metastases. A CT chest, abdomen and pelvis revealed numerous ground-glass and solid nodules in the lungs. Lower extremity duplex and transesophageal echocardiogram were negative. Serial blood cultures and serologies for cryptococcus and histoplasmosis, antineutrophil cytoplasmic antibody (ANCA, antinuclear antibody (ANA, rheumatoid factor (RF, cryoglobulin, and antiglomerular basement membrane (anti-GBM antibodies were all negative. CT guided lung biopsy was positive for Thioflavin T amyloid deposits. Brain biopsy was positive for eosinophilic material (similar to the lungs but negative for Thioflavin T stain. The patient's clinical status continued to deteriorate with cold cyanotic fingers developing on day 12 and a health care acquired pneumonia, respiratory failure, and fungemia on day 18. On day 29, family withdrew life support and denied any autopsies. Conclusion. Described is an atypical course of MGUS complicated by amyloidosis of the lung and nonamyloid eosinophilic deposition in the brain. As MGUS might be complicated by diseases such as amyloidosis and multiple myeloma, a scheduled follow-up of these patients is always

  10. Rearreglos de genes de cadenas pesadas de las inmunoglobulinas en las gammapatías monoclonales Immunoglobulin heavy chain gene rearrangements in the monoclonal gammopathies

    Directory of Open Access Journals (Sweden)

    Andrea Bosaleh

    2005-06-01

    gammopathies of unknown significance (MGUS. MGUS present a monoclonal component with no signs of multiple myeloma, Waldenström macroglobulinemia, primary amyloidosis or other disorders. Pathological, radiological and clinical features are required for the diagnosis. Approximately 25% of patients with MGUS will become multiple myeloma, primary amiloidosis, macroglobulinemia, or other lymphoproliferative disease, which would be a premyelomatous condition. The objective of this study was to determine the clinical implications of immunophenotyping by flow cytometry and of the detection of clonality by molecular biology. A total of 32 patients were studied. Seven of them were diagnosed with multiple myeloma, and 25 with monoclonal gammopathy under study. These 32 patients were divided into four groups, based on their clinical data and flow cytometry outcome. In patients with non-diagnostic flow cytometry detection of immunoglobulin heavy chain gene rearrangements by PCR was performed, and monoclonality was found in 59% of the cases. The study of immunoglobulin heavy chain gene rearrangements by molecular biology allows a more sensitive detection of clonality.

  11. Arterial and venous thrombosis in patients with monoclonal gammopathy of undetermined significance: incidence and risk factors in a cohort of 1491 patients.

    Science.gov (United States)

    Za, Tommaso; De Stefano, Valerio; Rossi, Elena; Petrucci, Maria Teresa; Andriani, Alessandro; Annino, Luciana; Cimino, Giuseppe; Caravita, Tommaso; Pisani, Francesco; Ciminello, Angela; Torelli, Fabio; Villivà, Nicoletta; Bongarzoni, Velia; Rago, Angela; Betti, Silvia; Levi, Anna; Felici, Stefano; Gentilini, Fabiana; Calabrese, Elisabetta; Leone, Giuseppe

    2013-03-01

    Monoclonal gammopathy of undetermined significance (MGUS) has been associated with an increased risk of thrombosis. We carried out a retrospective multicentre cohort study on 1491 patients with MGUS. In 49 patients (3.3%) MGUS was diagnosed after a thrombotic event. Follow-up details for a period of at least 12 months after diagnosis of MGUS were obtained in 1238 patients who had no recent history of thrombosis (thrombosis, with an incidence of 2.5 arterial events and 1.9 venous events per 1000 patient-years. Multivariate analysis showed increased risks of arterial thrombosis in patients with cardiovascular risk factors [hazard ratio (HR) 4.92, 95%confidence interval (CI) 1.42-17.04], and of venous thrombosis in patients with a serum monoclonal (M)-protein level >16 g/l at diagnosis (HR 3.08, 95%CI 1.01-9.36). No thrombosis was recorded in patients who developed multiple myeloma (n = 50) or other neoplastic diseases (n = 21). The incidence of arterial or venous thrombosis in patients with MGUS did not increase relative to that reported in the general population for similarly aged members. Finally, the risk of venous thrombosis did increase when the M-protein concentration exceeded >16 g/l.

  12. Epidemiology of Monoclonal Gammopathy of Undetermined Significance (MGUS): The experience from the specialized registry of hematologic malignancies of Basse-Normandie (France).

    Science.gov (United States)

    Cabrera, Quentin; Macro, Margaret; Hebert, Benedikte; Cornet, Edouard; Collignon, Albert; Troussard, Xavier

    2014-08-01

    Multiple myeloma (MM) is the third most common haematologic malignancy in European countries, and is usually preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS). Therefore epidemiologic studies of MGUS are very limited in a population-based status. Here we report all new cases of MGUS exhaustively recorded by the Basse-Normandie Regional Registry for Hematologic Malignancies (a French region registry) between January 1997 and December 2005, and analyze outcome of patients until 2009 in term of evolution in MM or death. All cases were analyzed by an expert file review, and MGUS diagnosis was retained for: evidence of a monoclonal component <30 g/l and no CRAB criteria (hyperCalcemia, renal insufficiency, anemia, bone lesions). We showed that the world standardized incidence rate (WSR) for MGUS was 3.76 ± 0.26 per 100,000 inhabitants, increasing regularly with age, and that the median overall survival (OS) was 115.9 months (CI 95%: 10.5-130.2 months) with 78.3% patients alive at 5 years (CI 95%: 74.1-81.9%). We also observed a rate of progression to multiple myeloma of 1.41% per year, concordant with previous reports in a reallife exhaustive registry.

  13. Analysis of Monoclonal Antibodies in Human Serum as a Model for Clinical Monoclonal Gammopathy by Use of 21 Tesla FT-ICR Top-Down and Middle-Down MS/MS

    Science.gov (United States)

    He, Lidong; Anderson, Lissa C.; Barnidge, David R.; Murray, David L.; Hendrickson, Christopher L.; Marshall, Alan G.

    2017-05-01

    With the rapid growth of therapeutic monoclonal antibodies (mAbs), stringent quality control is needed to ensure clinical safety and efficacy. Monoclonal antibody primary sequence and post-translational modifications (PTM) are conventionally analyzed with labor-intensive, bottom-up tandem mass spectrometry (MS/MS), which is limited by incomplete peptide sequence coverage and introduction of artifacts during the lengthy analysis procedure. Here, we describe top-down and middle-down approaches with the advantages of fast sample preparation with minimal artifacts, ultrahigh mass accuracy, and extensive residue cleavages by use of 21 tesla FT-ICR MS/MS. The ultrahigh mass accuracy yields an RMS error of 0.2-0.4 ppm for antibody light chain, heavy chain, heavy chain Fc/2, and Fd subunits. The corresponding sequence coverages are 81%, 38%, 72%, and 65% with MS/MS RMS error 4 ppm. Extension to a monoclonal antibody in human serum as a monoclonal gammopathy model yielded 53% sequence coverage from two nano-LC MS/MS runs. A blind analysis of five therapeutic monoclonal antibodies at clinically relevant concentrations in human serum resulted in correct identification of all five antibodies. Nano-LC 21 T FT-ICR MS/MS provides nonpareil mass resolution, mass accuracy, and sequence coverage for mAbs, and sets a benchmark for MS/MS analysis of multiple mAbs in serum. This is the first time that extensive cleavages for both variable and constant regions have been achieved for mAbs in a human serum background.

  14. Analysis of Monoclonal Antibodies in Human Serum as a Model for Clinical Monoclonal Gammopathy by Use of 21 Tesla FT-ICR Top-Down and Middle-Down MS/MS

    Science.gov (United States)

    He, Lidong; Anderson, Lissa C.; Barnidge, David R.; Murray, David L.; Hendrickson, Christopher L.; Marshall, Alan G.

    2017-02-01

    With the rapid growth of therapeutic monoclonal antibodies (mAbs), stringent quality control is needed to ensure clinical safety and efficacy. Monoclonal antibody primary sequence and post-translational modifications (PTM) are conventionally analyzed with labor-intensive, bottom-up tandem mass spectrometry (MS/MS), which is limited by incomplete peptide sequence coverage and introduction of artifacts during the lengthy analysis procedure. Here, we describe top-down and middle-down approaches with the advantages of fast sample preparation with minimal artifacts, ultrahigh mass accuracy, and extensive residue cleavages by use of 21 tesla FT-ICR MS/MS. The ultrahigh mass accuracy yields an RMS error of 0.2-0.4 ppm for antibody light chain, heavy chain, heavy chain Fc/2, and Fd subunits. The corresponding sequence coverages are 81%, 38%, 72%, and 65% with MS/MS RMS error 4 ppm. Extension to a monoclonal antibody in human serum as a monoclonal gammopathy model yielded 53% sequence coverage from two nano-LC MS/MS runs. A blind analysis of five therapeutic monoclonal antibodies at clinically relevant concentrations in human serum resulted in correct identification of all five antibodies. Nano-LC 21 T FT-ICR MS/MS provides nonpareil mass resolution, mass accuracy, and sequence coverage for mAbs, and sets a benchmark for MS/MS analysis of multiple mAbs in serum. This is the first time that extensive cleavages for both variable and constant regions have been achieved for mAbs in a human serum background.

  15. Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis

    Directory of Open Access Journals (Sweden)

    Yijuan Sun

    2012-01-01

    Full Text Available AL amyloidosis complicating monoclonal gammopathy of undetermined significance (MGUS has usually a predominant glomerular deposition of lambda light chain. Heavy proteinuria is one of its cardinal manifestations. A 78-year-old man with a 9-year history of IgG kappa light-chain-MGUS and normal urine protein excretion developed severe renal failure. Serum levels of kappa light chain and serum IgG had been stable while proteinuria was absent throughout the nine-year period. For the first eight years, he had stable stage III chronic kidney disease attributed to bladder outlet obstruction secondary to prostatic malignancy. In the last year, he developed progressive serum creatinine elevation, without any increase in the serum or urine levels of paraproteins or any sign of malignancy. Renal ultrasound and furosemide renogram showed no evidence of urinary obstruction. Renal biopsy revealed AL amyloidosis, with reactivity exclusive for kappa light chains, affecting predominantly the vessels and the interstitium. Glomerular involvement was minimal. Melphalan and prednisone were initiated. However, renal function continues deteriorating. Deposition of AL kappa amyloidosis developing during the course of MGUS predominantly in the wall of the renal vessels and the renal interstitium, while the involvement of the glomeruli is minimal, leads to progressive renal failure and absence of proteinuria. Renal biopsy is required to detect both the presence and the sites of deposition of renal AL kappa light chain amyloidosis.

  16. Clinical Significance of Monoclonal Gammopathy with Undetermined Significance-Review%意义未明的单克隆γ球蛋白病的临床意义

    Institute of Scientific and Technical Information of China (English)

    王学文; 李锋

    2010-01-01

    意义未明的单克隆γ球蛋白病(monoclonal gammopathy with undetermined significance,MGUS)是最常见的浆细胞病,为无症状的前期恶性疾惠.呈亚临床病症.每年约有1.5%的MGUS患者进展为多发性骨髓瘤(MM)或相关的浆细胞病.累积的进展概率10年10%,20年21%和25年26%.与匹配的对照人群相比,其进展为MM、华氏巨球蛋白血症(WM)、AL淀粉样变和淋巴瘤的危险分别增加25倍、46倍、8.4倍和2.4倍.MGUS与广泛范围的其他恶性和非恶性疾病相关.表明MGUS不总是无害或良性.确定MGUS进展的高危因素,推迟或预防其进展及其对高危进展因素的靶向和改善生存期均是本综述探索和讨论的热点论题.

  17. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: a review of the current understanding of epidemiology, biology, risk stratification, and management of myeloma precursor disease.

    Science.gov (United States)

    Agarwal, Amit; Ghobrial, Irene M

    2013-03-01

    The term monoclonal gammopathy of undetermined significance (MGUS) was coined in 1978. The recent advances in our knowledge about MGUS and smoldering multiple myeloma (SMM) have helped us better understand the pathogenesis of myeloma. It seems that myeloma evolves from a precursor state in almost all cases. We do not completely understand the multistep process from the precursor state to myeloma, but studies like whole genome sequencing continue to improve our understanding of this process. The process of transformation may not be linear acquisition of changes, but rather a branched heterogeneous process. Clinical features that are prognostic of rapid transformation have been identified, but no specific molecular markers have been identified. Even with recent advances, multiple myeloma remains an incurable disease in the vast majority, and intervening at the precursor state provides a unique opportunity to alter the natural history of the disease. A limitation is that a vast majority of patients with precursor disease, especially low-risk MGUS, will never progress to myeloma in their lifetime, and treating these patients is not only unnecessary but may be potentially harmful. The challenge is to identify a subset of patients with the precursor state that would definitely progress to myeloma and in whom interventions will have a meaningful impact. As our understanding of the molecular and genetic processes improves, these studies will guide the selection of high-risk patients more appropriately and ultimately direct a tailored management strategy to either delay progression to symptomatic myeloma or even "cure" a person at this premalignant stage.

  18. The diagnostic value of SE MRI and DWI of the spine in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Dutoit, Julie C.; Vanderkerken, Matthias A.; Dochy, Frederick; Verstraete, Koenraad L. [Ghent University Hospital, Department of Radiology, Ghent (Belgium); Anthonissen, Joris [Ghent University, Ghent (Belgium)

    2014-11-15

    To evaluate DWI of the bone marrow in the differentiation of monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma (SMM) and multiple myeloma (MM). The retrospective study includes 64 patients with MGUS, 27 with SMM, 64 with new MM and 12 controls. Signal intensity (SI) of spinal SE-MRI and DWI (b0-1000) as well as apparent diffusion coefficients (ADC) were measured in the T10 and L3. Qualitative assessment of b-images was performed by one experienced radiologist. ADC600 and ADC1000 are the best ADC values in differentiating patient groups (p < 0.030). SIT2, SIb1000 and ADC1000 are higher and SIT1 lower in L3 compared to T10 (p < 0.050). All quantitative parameters of L3 can differentiate significantly between MGUS and MM (p < 0.050) and between patients with percentage plasma cells (PC%) between 0-10 % compared to >50 % (p = 0.001). Only SIT2 for L3 can differentiate MGUS from SMM (p = 0.044) and PC%0-10 from PC%10-25 (p = 0.033). Qualitative interpretation of b1000 images allows differentiating MM patients from those with MGUS or SMM (p < 0.001). Spinal SE-MRI can differentiate among MGUS, SMM, MM and control subjects. DWI based on the SI on b1000 images and ADC values is increased in MM compared to MGUS and SMM. Qualitative assessment of b-images can differentiate MM from MGUS or SMM. (orig.)

  19. Secondary monoclonal gammopathy of undetermined significance is frequently associated with high response rate and superior survival in patients with plasma cell dyscrasias.

    Science.gov (United States)

    Zou, Dehui; An, Gang; Zhu, Guoqing; Wang, Jinhong; Shi, Lihui; Meng, Hengxing; Xu, Yan; Sui, Weiwei; Deng, Shuhui; Zhan, Fenghuang; Qiu, Lugui

    2014-03-01

    Secondary monoclonal gammopathy of undetermined significance (MGUS) is a special phenomenon that occurs during the treatment of multiple myeloma (MM). The incidence, biological characteristics, and prognostic value of secondary MGUS in patients with MM remain undefined. We proceed with a retrospective systematic review of serum immunofixation electrophoresis studies performed in 438 cases of patients with plasma cell dyscrasias, including 409 cases of newly diagnosed MM and 29 cases of primary plasma cell leukemia. Secondary MGUS was more common in patients with myeloma who had undergone stem cell transplantation than in those who had not (17 [29.8%] of 57 versus 5 [1.4%] of 352, P < .001). The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS were comparable. The complete response rates in patients with or without secondary MGUS were 81.8% and 21.8% respectively (P < .01). For the cohort as a whole, secondary MGUS was associated with significantly prolonged progression-free survival (median, 52.0 months versus 22.5 months; P = .002) and overall survival (median, not reached versus 35.0 months; P < .001). The presence of secondary MGUS retained independent prognostic value with a moderate impact on overall survival (hazard ratio .128 [95% confidence interval .018 to .922]; P = .041) in the multivariate Cox regression model. However, when analysis was restricted to patients undergoing stem cell transplantation, no statistical differences in progression-free survival and overall survival were found. In conclusion, we observe that secondary MGUS was frequently observed in MM patients after transplantation and conferred a survival prolongation. The favorable survival in patients with secondary MGUS may be explained by beneficial effect from myeloablative therapy. Copyright © 2014 American Society for Blood and Marrow Transplantation. All rights reserved.

  20. History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study.

    Science.gov (United States)

    Lindqvist, Ebba K; Landgren, Ola; Lund, Sigrún H; Turesson, Ingemar; Hultcrantz, Malin; Goldin, Lynn; Björkholm, Magnus; Kristinsson, Sigurdur Y

    2017-02-01

    Multiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls. Cox regression was used to calculate hazard ratios (HRs) for overall survival with 95 % confidence intervals (CIs). In patients with MM and a prior autoimmune disease, the risk of death was significantly increased, HR = 1.2 (95 % CI 1.2-1.3) compared to MM patients with no history of autoimmunity. In MGUS patients, a prior autoimmune disease was associated with a significantly 1.4-fold elevated risk of death (95 % CI 1.3-1.4). When analyzing different types of autoimmune diseases, a history of ulcerative colitis had a stronger impact on survival in MM than in controls. Our findings that a history of autoimmune disease has a negative impact on survival in MM and MGUS could be due to shared underlying common genetic factors, or that patients with a history of autoimmunity develop more severe cases of MM and MGUS, or cumulative comorbidity in the individual. Our results suggest that more attention should be paid to comorbidity as a prognostic factor in MGUS and MM, and underlines the need for studies aimed at tailoring therapy according to comorbidity.

  1. A case of severe chronic inflammatory demyelinating polyradiculoneuropathy with monoclonal gammopathy of undetermined significance with alternating immunoglobulin class to IgM from IgA.

    Science.gov (United States)

    Hayashi, Shintaro; Nagamine, Shun; Makioka, Kouki; Kusunoki, Susumu; Okamoto, Koichi

    2016-09-29

    A 71-year-old woman with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with IgA-λ monoclonal gammopathy of undetermined significance (MGUS) showed the acute development of tetraplegia, respiratory failure, and a marked fluctuation of the blood pressure. Intravenous (IV) high-dose steroid therapy (methylprednisolone: 1 g/day × 3 days), followed by oral prednisolone (PSL) (40 mg/day), and IV immunoglobulin (IVIg, 0.4 g/kg/day × 5 days) administrations resulted in the amelioration of these symptoms. However, they soon relapsed, which eventually led to complete tetraplegia and the need for mechanical ventilation. At this time, serum components of IgA-λ and IgM-λ were biclonally positive. Seven courses of plasma exchange and the alternative administration of dexamethasone (12 mg/day) and methtorexate (15 mg/week) were conducted, but with no significant improvement. Nine months after admission, she showed totally-locked in syndrome. Cryo-preserved serum obtained at this time showed high titers of IgM class antibodies against ganglioside (GD3 +++, GT1a ++++, GT1b ++, GQ1b +++, and GD1b +++), which had been negative on admission. Biopsy of the left sural nerve showed moderate reductions of large and small myelinated fibers with no inflammation, no depositions of amyloid, IgG, IgA, or IgM, and teased fiber findings revealed neither myelin ovoids nor segmental demyelination. Alternatively, melphalan at 5 mg and PSL at 32 mg were administered, with no amelioration, while serum IgA-λ monoclonal protein diminished, and IgM-λ M protein positivity was continuously observed. She frequently developed sepsis; therefore, we could no longer continue any immunosupressive therapies, but monthly IVIg administrations were given. Twelve months after admission, her neurological symptoms gradually improved and she was weaned off of mechanical ventilation. Eighteen months after admission, her muscle strength corresponded to 2 on manual muscle testing

  2. Concurrent pyoderma gangrenosum and subcorneal pustular dermatosis in a patient with monoclonal IgA/λ gammopathy

    Directory of Open Access Journals (Sweden)

    Ya-Wen Hsiao

    2011-12-01

    Full Text Available Subcorneal pustular dermatosis (SPD and pyoderma gangrenosum (PG are two neutrophilic dermatoses. Coexistence of these diseases in the same patient is rare and may be a strong indicator of IgA dysglobulinemia. We describe a 69-year-old man who presented with waxing and waning flaccid pustules covering his trunk and four limbs. Poorly healing ulcerations, which usually progressed into larger nodules after debridement, were also noted. Repeated cultures were negative for bacteria, and the patient was diagnosed with SPD and PG. Serum protein electrophoresis and immunofixation revealed a monoclonal IgA lambda protein. A subsequent bone marrow biopsy revealed a normocellular marrow. While PG and SPD can occur individually in a variety of associated diseases, such as rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease or infection; however, their coexistence is strongly indicative of IgA dysglobulinemia.

  3. Plasma exchange and chlorambucil in polyneuropathy associated with monoclonal IgM gammopathy. IgM-associated Polyneuropathy Study Group.

    Science.gov (United States)

    Oksenhendler, E; Chevret, S; Léger, J M; Louboutin, J P; Bussel, A; Brouet, J C

    1995-01-01

    The study compared chlorambucil alone with chlorambucil in combination with plasma exchange in patients with polyneuropathy associated with monoclonal IgM. Forty four patients were prospectively randomly assigned, in a comparative open trial, to receive either 0.1 mg/kg/day chlorambucil orally, for 12 months or chlorambucil associated with 15 courses of plasma exchange, during the first four months of treatment. They were evaluated by a neuropathy disability score and nerve conduction studies. No difference was found between the two treatment groups. The average neuropathy disability score improved by 2.1 points from baseline (21.0 to 18.9) in the chlorambucil group and by 1.8 points (20.4 to 18.6) in the chlorambucil + plasma exchange group (P = 0.70). The mean motor nerve conduction velocity decreased from 20.0 to 18.2 m/s in the chlorambucil group and increased from 20.5 to 22.5 m/s in the chlorambucil + plasma exchange group (P = 0.51). A slight improvement of the sensory component of the neuropathy disability score (from 10.5 to 8.3) was noted in both groups (P = 0.01). At the end of the study and according to self evaluation, 15 patients--eight from the chlorambucil group and seven from the chlorambucil + plasma exchange group--reported clinical improvement, whereas 15--eight from the chlorambucil group and seven from the chlorambucil + plasma exchange group--reported clinical worsening. Neuropathy remained stable in the others. Thus plasma exchange seemed to confer no additional benefit in the treatment of polyneuropathy associated with monoclonal IgM. PMID:7673949

  4. Renal small B-cell lymphoma with plasmacytic differentiation presenting with monoclonal gammopathy and disseminated intravascular coagulation syndrome

    Directory of Open Access Journals (Sweden)

    Paula de Oliveira Pádua Prestes

    2013-10-01

    Full Text Available Primary renal lymphomas are very rare. However, the kidney may be a site of metastasis, usually from a disseminated aggressive lymphoma. A 58-year-old woman was brought to the medical facility due to acute mental confusion, severe hypotension, septic shock, and signs of disseminated intravascular coagulation. Laboratory tests showed severe leukopenia, renal failure, altered liver function, and elevated serum lactate dehydrogenase levels. Protein electrophoresis revealed hypergammaglobulinemia with a monoclonal peak of IgG lambda. The clinical outcome was fulminant and the patient died less than 24 hours after admission. Autopsy revealed an indolent B-cell lymphoma with extensive plasmacytic differentiation infiltrating the right renal sinus and involving the submandibular and sublingual glands, cervical and peri-aortic lymph nodes, multiple microscopic foci in pituitary and adrenal glands, lung, breast, liver, thyroid, and bone marrow. Numerous IgG4-positive plasma cells were detected by immunohistochemistry although other histological features of IgG4-related disease were missing. There was also extensive hemorrhagic necrosis of the adrenal glands and purulent cystitis, which was probably responsible for the septic shock. The authors concluded that the kidney was most likely the primary site of the indolent lymphoma, as that was the site with the largest tumor mass. Infiltration of other organs was considered as dissemination of the disease. The differential diagnosis with mucosa-associated lymphoid tissue and lymphoplasmacytic lymphoma is discussed.

  5. The expression of osteopontin and vascular endothelial growth factor in correlation with angiogenesis in monoclonal gammopathy of undetermined significance and multiple myeloma.

    Science.gov (United States)

    Babarović, Emina; Valković, Toni; Budisavljević, Ivana; Balen, Ivan; Štifter, Sanja; Duletić-Načinović, Antica; Lučin, Ksenija; Jonjić, Nives

    2016-06-01

    Several studies have shown a gradual increase in the extent of bone marrow angiogenesis in various stages of proliferative plasma cell disorders, from monoclonal gammopathy of undetermined significance (MGUS) to active multiple myeloma (MM). The main aim of this study was to evaluate tumor angiogenesis parameters in detail and to correlate them with the expression of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in the bone marrow of patients with MGUS and MM. In addition, we wanted to determine their prognostic significance in active MM. Ninety-five patients were enrolled in the study: 14 diagnosed with MGUS, 13 with asymptomatic myeloma (AMM) and 68 with active MM. Computer assisted image analysis was used to determine the angiogenesis parameters, the quantity of microvessels per 1mm(2) (MVD), the area occupied by microvessels per 1mm(2) and the percentage of microvessel area in total section area (TVA). Double immunohistochemical methods CD138+VEGF and CD138+OPN were used to evaluate expression of these proteins in plasma cells, and OPN was also analyzed for its interstitial expression (iOPN). A significant positive correlation was determined between VEGF and iOPN with angiogenic parameters in the MGUS stage of the disease. In advanced stages of the disease, a significant negative correlation was recorded between OPN and iOPN with parameters of angiogenesis. Overall survival was significantly shorter for patients with negative iOPN (p=0.002) and higher angiogenic parameters, MVD (p=0.009), TVA (p=0.008) and area of microvessels per 1mm(2) (p=0.02). Positive VEGF expression in our model predicted a better three-year survival of patients with active MM (OR: 5.25, p=0.03; HR: 0.44, p=0.04). The results of our study suggested a possible key role of VEGF and OPN in the induction of angiogenesis in early-stage disease. Copyright © 2016 Elsevier GmbH. All rights reserved.

  6. Chronic hepatitis C virus infection and lymphoproliferative disorders: mixed cryoglobulinemia syndrome, monoclonal gammopathy of undetermined significance, and B-cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Caviglia, Gian Paolo; Sciacca, Claudio; Abate, Maria Lorena; Olivero, Antonella; Rosso, Chiara; Touscoz, Giovanni Antonio; Ciancio, Alessia; Rizzetto, Mario; Smedile, Antonina

    2015-04-01

    Chronic hepatitis C (CHC) has been associated with lymphoproliferative disorders (LPD) such as mixed cryoglobulinemia syndrome (MCS), monoclonal gammopathy of undetermined significance (MGUS), and B-cell non-Hodgkin lymphoma (B-NHL). The aim of the present study is to assess MCS, MGUS, and B-NHL prevalence in a cohort of CHC-infected patients and to evaluate the association of demographic, clinical, and virologic factors with the presence of LPDs. A total of 121 CHC patients with LPDs (50 M, 71 F; mean age 61.5 ± 11.8) and 130 CHC patients without extrahepatic manifestations (60 M, 70 F; mean age 60.4 ± 9.2) were retrospectively enrolled from a cohort of 1313 CHC patients between January 2006 and December 2013. Patients with LPDs included: 25 patients with MCS (9 M, 16 F; mean age 60.2 ± 1.4), 55 patients with MGUS (18 M, 37 F; mean age 61.3 ± 12.1), and 41 patients with B-NHL (23 M, 18F; mean age 62.5 ± 11.0) RESULTS: Patients with MCS (25/1313; 1.9%), MGUS (55/1313; 4.2%), and B-LNH (41/1313; 3.1%) did not differ in age, severity of liver disease, HCV genotype, and response to antiviral therapy. Using multivariate logistic regression analysis, a positive association was found between the presence of cirrhosis and MGUS (odds ratio [OR] = 2.8924, 95% confidence interval [CI] 1.2693-6.5909; P = 0.012) and between cirrhosis and B-NHL (OR = 3.9407, 95% CI 1.7226-9.0153; P = 0.001), whereas no association with MCS diagnosis emerged. Despite the pathogenetic mechanism of HCV-associated LPDs is still unclear, cirrhosis is an additional risk factor for the development of lymphoproliferative disorders in patients with chronic HCV infection. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  7. Clues to pathogenesis of Waldenström macroglobulinemia and immunoglobulin M monoclonal gammopathy of undetermined significance provided by analysis of immunoglobulin heavy chain gene rearrangement and clustering of B-cell receptors.

    Science.gov (United States)

    Varettoni, Marzia; Zibellini, Silvia; Capello, Daniela; Arcaini, Luca; Rossi, Davide; Pascutto, Cristiana; Rattotti, Sara; Mangiacavalli, Silvia; Pochintesta, Lara; Gotti, Manuel; Gaidano, Gianluca; Cazzola, Mario

    2013-11-01

    We characterized immunoglobulin heavy chain (IGH) gene rearrangements and searched for clusters of stereotyped B-cell receptors in 123 patients with Waldenström macroglobulinemia (WM; n = 59) or immunoglobulin M monoclonal gammopathy of undetermined significance (IgM-MGUS) (n = 64). A productive monoclonal IGHV-D-J rearrangement was obtained in 99/123 patients (80%). Immunoglobulin heavy chain variable (IGHV) genes were mutated in 94/99 patients (95%) with a median somatic hypermutation rate of 6.7% (2.1-14.5). Compared with the normal B-cell repertoire, patients with WM/IgM-MGUS showed an over-representation of the IGHV3 subgroup (83% vs. 55%, p < 0.0001) and an under-representation of IGHV1 (7% vs. 14%, p = 0.04) and IGHV4 (7% vs. 23%, p = 0.0001) subgroups. At the gene level, in WM/IgM-MGUS there was an over-representation of IGHV3-23 (24% vs. 12%, p = 0.0003), IGHV3-64 (3% vs. < 1%, p = 0.003), IGHV3-7 (12% vs. 4%, p = 0.0001) and IGHV3-74 (9% vs. 2%, p < 0.0001), while IGHV4-39 was never used (0 vs. 5%, p = 0.03). Intra-WM/IgM-MGUS search for HCDR3 similarity showed no association fulfilling criteria for stereotyped receptors. WM/IgM-MGUS sequences were unrelated to known chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL) or mantle cell lymphoma (MCL) subsets. In conclusion, the IGHV gene usage in WM and IgM-MGUS is remarkably biased as compared to the normal B-cell repertoire. WM and IgM-MGUS-specific HCDR3 clusters do not occur with a frequency detectable with currently available databases, not supporting a B-cell receptor-driven pathogenesis in WM and IgM-MGUS.

  8. Association between metformin use and transformation of monoclonal gammopathy of undetermined significance to multiple myeloma in U.S. veterans with diabetes mellitus: a population-based cohort study

    Science.gov (United States)

    Chang, Su-Hsin; Luo, Suhong; O’Brian, Katiuscia K.; Thomas, Theodore S.; Colditz, Graham A.; Carlsson, Nils P.; Carson, Kenneth R.

    2015-01-01

    Background Multiple myeloma (MM) is one of the most common hematologic malignancies in the United States and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Methods A retrospective cohort of patients in the U.S. Veterans Health Administration database diagnosed with MGUS between 1, October, 1999 and 31, December, 2009 and diabetes mellitus prior to their MGUS diagnosis was identified and followed through 6, August, 2013. Patient-level clinical data were reviewed to verify diagnoses and to abstract data on size of baseline M-protein and type of MGUS, i.e., immunoglobulin (Ig) subtype or light-chain, when available. Metformin users were defined as patients that were prescribed metformin for at least 4 years, with no single break between consecutive prescriptions ≥6 months. Kaplan-Meier curves and Cox models were used to analyze the association between metformin use and the progression of MGUS to MM. Findings The analytic cohort consisted of 2,003 MGUS patients with a median follow-up time of 69 months. Within the analytic cohort, 463 metformin users (23·1%) were identified. Among the metformin users, 13 patients progressed to MM, while 74 patients progressed to MM among the non-metformin users. Metformin use was associated with a reduced risk of transformation to MM (Hazard ratio, HR: 0·47; 95% confidence interval, CI: 0·25–0·87). Interpretation For diabetics diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of transformation of MGUS to MM. Prospective studies are required to determine whether this association is causal and whether these results can be extrapolated to non-diabetics. PMID:26034780

  9. Researche progress on monoclonal gammopathy of undetermined significance and asymptomatic multiple myeloma%意义未明的单克隆丙种球蛋白病及无症状多发性骨髓瘤的研究进展

    Institute of Scientific and Technical Information of China (English)

    姜鸾

    2012-01-01

    目前人们对意义未明的单克隆丙种球蛋白病( MGUS)及无症状多发性骨髓瘤(MM)这两种前期病变的认识尚不足,对近年来这两种疾病在诊断、危险分层以及治疗观点上的进展进行综述.%Nowadays there is still an insufficient understanding of monoclonal gammopathy of undetermined significance(MGUS) and asymptomatic multiple myeloma,which are considered as multiple myeloma (MM) precursor diseases. In this review, the advances in diagnosis, risk-stratification as well as views on the treatment of the two diseases were presented.

  10. Utility of testing for monoclonal bands in serum of patients with suspected osteoporosis

    DEFF Research Database (Denmark)

    Abrahamsen, B.; Andersen, Ivan; Christensen, Susanne S.

    2005-01-01

    of multiple myeloma diagnosed. All patients with multiple myeloma had a history of fragility fractures. If lymphoma was included as a target condition, the specificity increased to 95.3% and the positive predictive value increased to 23.5%. Monoclonal gammopathy of undetermined significance was diagnosed...... or monoclonal gammopathy of undetermined significance....

  11. Biclonal Gammopathy in Chronic Lymphocytic Leukemia: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Nafila Al-Riyami

    2015-05-01

    Full Text Available Monoclonal gammopathies are frequently seen in B-cell malignancies. Monoclonal proteins are seen in a significant proportion of patients with chronic lymphocytic leukemia (CLL, which is a clonal disorder of mature B cells. The use of more sensitive laboratory methods has enabled the detection of monoclonal proteins or light chains in the serum and/or urine in the majority of these patients. The presence of some of these monoclonal proteins may explain the different autoimmune phenomena that are associated with this disease. Some reports indicate that the finding of monoclonal proteins has a negative impact on patients’ survival. The presence of two different monoclonal proteins (i.e. biclonal gammopathy is on the other hand rare. Most of the reported cases in the literature are of patients with plasma cell disorders. In this report, we describe a rare occurrence of biclonal gammopathy in a patient with CLL. Serum protein electrophoresis and immunofixation, which were negative at the time of initial diagnosis, showed biclonal immunoglobin A (IgA kappa and IgA lambda during the course of the disease. The patient’s disease showed steady progression, despite multiple treatments. Although this could just be the result of using more sensitive laboratory techniques, biclonal gammopathy in this patient likely reflects the evolution of another clone, which would explain the encountered resistance to therapy. Because of paucity of reports, the impact of biclonal gammopathies in such patients is not known and an effort to collectively report the presentation and outcome of these patients is needed to further understand the pathophysiology and clinical significance of such a finding.

  12. Calorimetric features of IgM gammopathies. Implication for patient’s diagnosis and monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Krumova, Sashka; Todinova, Svetla; Danailova, Avgustina [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia (Bulgaria); Petkova, Violeta; Dimitrova, Keranka; Gartcheva, Lidia [National Specialized Hospital for Active Treating of Haematological Diseases, Sofia 1756 (Bulgaria); Taneva, Stefka G., E-mail: stefka.germanova@ehu.es [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 21, 1113 Sofia (Bulgaria); Unidad de Biofísica (CSIC-UPV/EHU) and Departamento de Bioquímica y Biología Molecular, Universidad del País Vasco, 48080 Bilbao (Spain)

    2015-09-10

    Highlights: • DSC reveals distinct calorimetric features for IgM gammopaties. • Calorimetry sets of IgM multiple myeloma and Waldenström’s macroglobulinemia patients. • DSC features correlate with the level of involved IgM heavy/light chains. • DSC and “Heavylite” are complementary methods for patients diagnostics/monitoring. - Abstract: The serum proteome of patients featuring immunoglobulin M (IgM) gammopathy and diagnosed as having IgM multiple myeloma or Waldenström’s macroglobulinemia was characterized by differential scanning calorimetry and HevyLite™ (HLC) assay. The thermodynamic properties of the thermograms and their deviation from the typical healthy thermogram were found to correlate with the monoclonal protein concentration and the level of the involved (monoclonal) IgM heavy/light chains. Patients monitoring during treatment showed that the variations in the shape of the DSC profiles corresponded to fluctuations of the IgM heavy/light chain levels verifying the two parameters as non-invasive markers for disease progression.

  13. 意义未明的单克隆丙种球蛋白血症和冒烟型骨髓瘤:生物学特征与早期治疗策略%Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies

    Institute of Scientific and Technical Information of China (English)

    菅原; 严冬; 陈文明

    2014-01-01

    Researches on monoclonal gammopathy of undetermined significance (MGUS) and smoldering muhiple myeloma (SMM) are at a low level although their incidence is high.This review discusses curent biological insights in MGUS/SMM and discusses how the integration of novel biological markers,molecular imaging,and clinical monitoring of MGUS/SMM could facilitate the development of early treatment strategies for high-risk SMM (early myeloma) patients in the future.%尽管意义未明的单克隆丙种球蛋白血症(MGUS)与冒烟型骨髓瘤(SMM)在人群中的发生率并不低,但是相关研究较少.文章对MGUS/SMM的生物学研究进展进行了概述,并讨论了MGUS/SMM的危险分层、标志物与高危SMM(早期多发性骨髓瘤)患者的早期治疗策略.

  14. Occurrence of Double Monoclonal Bands on Protein Electrophoresis: An Unusual Finding.

    Science.gov (United States)

    Srinivasan, Vishrut K; Bhagat, Priyanka; Bansal, Frainey; Chhabra, Seema

    2016-06-01

    Various techniques of protein electrophoresis are used for detection of monoclonal proteins/paraproteins in serum and/or urine of patients with monoclonal gammopathies. These are detected as the so-called 'M' bands (monoclonal bands) on serum protein electrophoresis and/or immunofixation electrophoresis. In most cases, a single M-band is detected. However, more than one M-band can be detected in the samples of a minor proportion of patients. This condition is termed as 'double gammopathy' or 'biclonal gammopathy'. A knowledge of such an unusual occurrence is essential for recognition and appropriate interpretation of this entity.

  15. Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia): A Preliminary Clinical Study.

    Science.gov (United States)

    Golombick, Terry; Diamond, Terrence H; Manoharan, Arumugam; Ramakrishna, Rajeev

    2016-06-01

    Hypothesis Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies.

  16. Multiple myeloma and multiple plasmacytomas associated with free gamma heavy chain, free kappa light chain and IgGk paraproteins: an unusual triple gammopathy.

    Science.gov (United States)

    Deighan, William I; O'Kane, Maurice J; McNicholl, Feargal P; Keren, David F

    2016-11-01

    Multiple myeloma is a malignant plasma cell dyscrasia that is becoming more prevalent in an increasingly ageing population. It is a complex disease with clinical phases ranging from the premalignant monoclonal gammopathy of undetermined significance to asymptomatic (smouldering) myeloma and then symptomatic myeloma; the latter occasionally terminating in the clonal proliferation of plasma cells outside the bone marrow. We present a patient whose clonally evolved disease from monoclonal gammopathy of undetermined significance to multiple myeloma demonstrated the presence of an unusual combination of monoclonal immunoproteins. Capillary electrophoresis demonstrated the presence of three paraproteins in the gamma region (γ-region), two of which were additional to the IgGk paraprotein which migrated in the slow γ-region at initial diagnosis. Subsequent isotypic identification of the new paraproteins was not possible by immunotyping and initial immunofixation studies failed to definitively characterize the monoclonal proteins. After reduction with beta-mercaptoethanol, two paraproteins were detected by both capillary and gel electrophoresis. However, only immunofixation was able to resolve three distinct monoclonal bands, confirming the presence of free monoclonal kappa light chains in the mid-gamma region and free monoclonal heavy chains in the fast gamma region. Triple gammopathies in themselves are uncommon; this case presents a very unusual combination of paraproteins which required various electrophoretical and immunochemical techniques to identify and characterize them. The change of electrophoretic signature from the monoclonal gammopathy of undetermined significance phase to the diagnosis of multiple myeloma suggested that a number of genetically distinct subclones were present in the pretreatment clonal evolution of the disease.

  17. Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

    Energy Technology Data Exchange (ETDEWEB)

    Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Oshita, Masatoshi; Ideno, Shoji [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Yunoki, Mikihiro [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Kuhara, Motoki [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano 396-0002 (Japan); Yamamoto, Naomasa [Department of Biochemistry, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima 963-8611 (Japan); Okuno, Yoshinobu [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa 768-0061 (Japan); Ikuta, Kazuyoshi, E-mail: ikuta@biken.osaka-u.ac.jp [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan)

    2009-09-11

    Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.

  18. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.

    Science.gov (United States)

    Ledgerwood, J E; Coates, E E; Yamshchikov, G; Saunders, J G; Holman, L; Enama, M E; DeZure, A; Lynch, R M; Gordon, I; Plummer, S; Hendel, C S; Pegu, A; Conan-Cibotti, M; Sitar, S; Bailer, R T; Narpala, S; McDermott, A; Louder, M; O'Dell, S; Mohan, S; Pandey, J P; Schwartz, R M; Hu, Z; Koup, R A; Capparelli, E; Mascola, J R; Graham, B S

    2015-12-01

    VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 μg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 μg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.

  19. An Autopsy Case of Amyotrophic Lateral Sclerosis with Waldenström Macroglobulinemia and Anti-MAG Gammopathy

    Directory of Open Access Journals (Sweden)

    Snejana Jurici

    2011-12-01

    Full Text Available We report the case of a 71-year-old woman with typical signs of bulbar amyotrophic lateral sclerosis (ALS associated with immunoglobulin M (IgM monoclonal gammopathy and anti-MAG (myelin-associated glycoprotein antibodies. This unusual association between ALS and anti-MAG antibodies has previously been reported in a single case. Our present case, at neuropathological examination, demonstrated no causative link between anti-MAG antibodies and ALS.

  20. IgM monoclonal gammopathy and neuropathy in two siblings

    DEFF Research Database (Denmark)

    Jensen, T S; Schrøder, H D; Jønsson, V;

    1988-01-01

    patients contained antibodies directed to bovine peripheral nerve myelin as determined by ELISA technique and to normal human peripheral nerve myelin as demonstrated by indirect immunofluorescence histochemistry. These siblings may have a genetic predisposition to the formation of autoantibodies...

  1. 以周围神经病为首发症状的意义未明的单克隆丙种球蛋白病临床特点及诊治分析%Clinical Features,Diagnosis and Treatment of Monoclonal Gammopathy of Undetermined Significance with Peripheral ;Neuropathy as the First Symptom

    Institute of Scientific and Technical Information of China (English)

    葛叶波; 郭谊; 章殷希; 丁美萍

    2014-01-01

    Objective To investigate the clinical features,laboratory findings and treatment monoclonal gammopathy of undetermined significance( MGUS)with peripheral neuropathy as its first symptom. Methods Four cases of MGUS with pe-ripheral neuropathy as its first symptom admitted to the neurology department of the Second Affiliated Hospital of Zhejiang Univer-sity School of Medicine from January 2012 to July 2013 were selected,and their clinical features,laboratory findings and treat-ment were retrospectively analyzed. Results The four patients were all middle-aged men with subacute or chronic onset between 40-50 years old. Four cases firstly presented respectively as numbness of lower limbs,numbness and weakness of lower limbs, weakness of four limbs and numbness and weakness of four limbs. The course of the disease lasted from three months to ten years. The blood routine,liver function,kidney function,serum potassium and serum calcium of the four patients were all within normal limits. All patients had increased Ig and different increased levels of protein in cerebrospinal fluid,and the Bence-Jonces protein was negative. The immunofixation electrophoresis tests revealed two cases of IgAλ type,one case of IgGλ type and one case of IgMλ type. One case showed increased serum λ light chain, and three cases showed increased serum β2 microglobu-lin. Bone marrow aspiration showed increased plasma cell,with some demonstrating abnormal and immature shape. The electro-myography examination showed the axonal damage in two cases and demyelination with axonal damage in the other two cases. One case out of the four patients was given traditional Chinese medicine treatment,and ultimately died of disease progression;two ca-ses were given thalidomide and prednisone therapy,and one case showed non-aggravated symptoms and one case had progressive disease;one case was given treatment of prednisone alone,and showed no development of the symptoms. Conclusion MGUS with peripheral

  2. Monoclonal paraprotein influences baseline B-cell repertoire diversity and perturbates influenza vaccination-induced B-cell response

    NARCIS (Netherlands)

    Tete, Sarah M.; Kipling, David; Westra, Johanna; de Haan, Aalzen; Bijl, Marc; Dunn-Walters, Deborah K.; Sahota, Surinder S.; Bos, Nicolaas A.

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. It is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examin

  3. Monoclonal paraprotein influences baseline B-cell repertoire diversity and perturbates influenza vaccination-induced B-cell response

    NARCIS (Netherlands)

    Tete, Sarah M.; Kipling, David; Westra, Johanna; de Haan, Aalzen; Bijl, Marc; Dunn-Walters, Deborah K.; Sahota, Surinder S.; Bos, Nicolaas A.

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) arises from a clonal expansion of plasma cells in the bone marrow, secreting monoclonal (M) paraprotein. It is associated with increased susceptibility to infections, which may reflect altered B-cell repertoire. To investigate this, we examin

  4. Characterisation of CD4 T cells in healthy and diseased koalas (Phascolarctos cinereus) using cell-type-specific monoclonal antibodies.

    Science.gov (United States)

    Mangar, Chandan; Armitage, Charles W; Timms, Peter; Corcoran, Lynn M; Beagley, Kenneth W

    2016-07-01

    The koala (Phascolarctos cinereus) is an arboreal herbivorous marsupial that is an Australian icon. Koalas in many parts of Australia are under multiple threats including habitat destruction, dog attacks, vehicular accidents, and infectious diseases such as Chlamydia spp. and the koala retrovirus (KoRV), which may contribute to the incidence of lymphoma and leukaemia in this species. Due to a lack of koala-specific immune reagents and assays there is currently no way to adequately analyse the immune response in healthy, diseased or vaccinated animals. This paper reports the production and characterisation of the first anti-koala CD4 monoclonal antibody (mAb). The koala CD4 gene was identified and used to develop recombinant proteins for mAb production. Fluorochrome-conjugated anti-CD4 mAb was used to measure the levels of CD4(+) lymphocytes collected from koala spleens (41.1%, range 20-45.1%) lymph nodes (36.3%, range 19-55.9%) and peripheral blood (23.8%, range 17.3-35%) by flow cytometry. Biotin-conjugated anti-CD4 mAb was used for western blot to determine an approximate size of 52 kDa for the koala CD4 molecule and used in immunohistochemistry to identify CD4(+) cells in the paracortical region and germinal centres of spleen and lymph nodes. Using the anti-CD4 mab we showed that CD4 cells from vaccinated, but not control, koalas proliferated following in vitro stimulation with UV-inactivated Chlamydia pecorum and recombinant chlamydial antigens. Since CD4(+) T cells have been shown to play a pivotal role in clearing chlamydial infection in both human and mouse infections, using this novel antibody will help determine the role CD4(+) T cells play in protection against chlamydial infection in koalas and also enhance our knowledge of how KoRV affects the koala immune system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Long-term follow-up of a population based cohort with monoclonal proteinaemia

    NARCIS (Netherlands)

    Schaar, Cees G.; le Cessie, Saskia; Snijder, Simone; Franck, Paul F. H.; Wijermans, Pierre W.; Ong, Cisca; Kluin-Nelemans, Hanneke

    2009-01-01

    Prospective studies on the risk of malignant transformation in patients with monoclonal gammopathy of undetermined significance (MGUS) and factors predictive of survival are lacking. The Dutch Comprehensive Cancer Centre West, comprising 1.6 million inhabitants, initiated a prospective hospital-base

  6. Does My Patient with a Serum Monoclonal Spike have Multiple Myeloma?

    OpenAIRE

    Bianchi, Giada; Ghobrial, Irene M.

    2012-01-01

    A monoclonal spike (M spike or paraprotein) on serum protein electrophoresis (SPEP) is a frequent finding in the general population and typically is pathognomonic of an asymptomatic, premalignant condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS occurs in around 3% of people older than 50 and is associated with a lifelong, low, yet non negligible, risk of progression to multiple myeloma (MM) or a related plasma cell dyscrasia. It is generally an incidental diagn...

  7. A First-in-Human Study To Assess the Safety and Pharmacokinetics of Monoclonal Antibodies against Human Cytomegalovirus in Healthy Volunteers.

    Science.gov (United States)

    Dole, Kiran; Segal, Florencia Pereyra; Feire, Adam; Magnusson, Baldur; Rondon, Juan C; Vemula, Janardhana; Yu, Jing; Pang, Yinuo; Pertel, Peter

    2016-05-01

    Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the function of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. Here, we evaluated the safety, tolerability, and pharmacokinetics of a single intravenous dose of LJP538 or LJP539 or their combination in healthy volunteers. Adverse events and laboratory abnormalities occurred sporadically with similar incidence between antibody and placebo groups and without any apparent relationship to dose. No subject who received antibody developed a hypersensitivity, infusion-related reaction or anti-drug antibodies. After intravenous administration, both LJP538 and LJP539 demonstrated typical human IgG1 pharmacokinetic properties, with slow clearances, limited volumes of distribution, and long terminal half-lives. The pharmacokinetic parameters were linear and dose proportional for both antibodies across the 50-fold range of doses evaluated in the study. There was no apparent impact on pharmacokinetics when the antibodies were administered alone or in combination. CSJ148 and the individual monoclonal antibodies were safe and well tolerated, with pharmacokinetics as expected for human immunoglobulin.

  8. Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.

    Science.gov (United States)

    Taylor, Claribel P; Tummala, Sanjeev; Molrine, Deborah; Davidson, Lisa; Farrell, Richard J; Lembo, Anthony; Hibberd, Patricia L; Lowy, Israel; Kelly, Ciaran P

    2008-06-25

    Recent data suggest that Clostridium difficile-associated diarrhea is becoming more severe and difficult to treat. Antibody responses to C. difficile toxin A are protective against symptomatic disease and recurrence. We examined the safety and pharmacokinetics (pk) of a novel neutralizing human monoclonal antibody against C. difficile toxin A (CDA1) in healthy adults. Five cohorts with 6 subjects each received a single intravenous infusion of CDA1 at escalating doses of 0.3, 1, 5, 10, and 20 mg/kg. Safety evaluations took place on days 1, 2, 3, 7, 14, 28, and 56 post-infusion. Samples for pk analysis were obtained before and after infusion, and at each safety evaluation. Serum CDA1 antibody concentrations and human anti-human antibody (HAHA) titers were measured with enzyme-linked immunosorbent assays. A noncompartmental model was used for pk analysis. Thirty subjects were enrolled. The median age was 27.5 yrs. There were no serious adverse events (AE) related to CDA1. Twenty-one of the 48 reported non-serious adverse events were possibly related to CDA1, and included transient blood pressure changes requiring no treatment, nasal congestion, headache, abdominal cramps, nausea, and self-limited diarrhea. Serum CDA1 concentrations increased with escalating doses: mean C(max) ranged from 6.82 microg/ml for the 0.3 mg/kg cohort to 511 microg/ml for the 20 mg/kg cohort. The geometric mean values of the half-life of CDA1 ranged between 25.3 and 31.8 days, and the volume of distribution approximated serum. No subject formed detectable HAHA titers. Administration of CDA1 as a single intravenous infusion was safe and well tolerated. C(max) increased proportionally with increasing doses. A randomized study of CDA1 in patients with C. difficile associated diarrhea is underway.

  9. Polyclonal gammopathy related to renal bleeding in a peritoneal dialysis patient

    Directory of Open Access Journals (Sweden)

    Eun-Mi Cho

    2013-07-01

    Full Text Available Polyclonal gammopathy represents the diffuse activation of B cells and is usually related to inflammation or immune-related diseases. However, the mechanisms leading to polyclonal gammopathy are essentially speculative. Generally, infectious, inflammatory, or various other reactive processes may be indicated by the presence of a broad-based peak or band in the gamma region on serum protein electrophoresis results. A 15-year-old girl, who had been receiving peritoneal dialysis, presented with polyclonal gammopathy and massive gross hematuria. Renal artery embolization was performed, after which the continuous bleeding subsided and albumin-globulin dissociation resolved. This is a rare case of polyclonal gammopathy related to renal bleeding.

  10. Monoclonal B lymphocytes with the characteristics of "indolent" chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts.

    Science.gov (United States)

    Rawstron, Andy C; Green, Michael J; Kuzmicki, Anita; Kennedy, Ben; Fenton, James A L; Evans, Paul A S; O'Connor, Sheila J M; Richards, Stephen J; Morgan, Gareth J; Jack, Andrew S; Hillmen, Peter

    2002-07-15

    Molecular and cellular markers associated with malignant disease are frequently identified in healthy individuals. The relationship between these markers and clinical disease is not clear, except where a neoplastic cell population can be identified as in myeloma/monoclonal gammopathies of undetermined significance (MGUS). We have used the distinctive phenotype of chronic lymphocytic leukemia (CLL) cells to determine whether low levels of these cells can be identified in individuals with normal complete blood counts. CLL cells were identified by 4-color flow cytometric analysis of CD19/CD5/CD79b/CD20 expression in 910 outpatients over 40 years old. These outpatients were age- and sex-matched to the general population with normal hematologic parameters and no evident history of malignant disease. CLL phenotype cells were detectable in 3.5% of individuals at low level (median, 0.013; range, 0.002- 1.458 x 10(9) cells/L), and represented a minority of B lymphocytes (median, 11%; range, 3%-95%). Monoclonality was demonstrated by immunoglobulin light-chain restriction in all cases with CLL phenotype cells present and confirmed in a subset of cases by consensus-primer IgH-polymerase chain reaction. As in clinical disease, CLL phenotype cells were detected with a higher frequency in men (male-to-female ratio, 1.9:1) and elderly individuals (2.1% of 40- to 59-year-olds versus 5.0% of 60- to 89-year-olds, P =.01). The neoplastic cells were identical to good-prognosis CLL, being CD5+23+20(wk)79b(wk)11a(-)22(wk)sIg(wk)CD38-, and where assessed had a high degree (4.8%-6.6%) of IgH somatic hypermutation. The monoclonal CLL phenotype cells present in otherwise healthy individuals may represent a very early stage of indolent CLL and should be useful in elucidating the mechanisms of leukemogenesis.

  11. Autoimmune manifestations in patients with multiple myeloma and monoclonal gammopathy of undetermined significance

    Directory of Open Access Journals (Sweden)

    Alexei Shimanovsky

    2016-12-01

    Conclusions: Future research is required to explore further the link between MGUS/MM and autoimmune disorders. Inflammation in the setting of autoimmunity may serve as a trigger for MGUS and MM. In addition, a common genetic susceptibility for developing both an autoimmune disease and MM/MGUS might also exist. Autoimmune hematologic and rheumatologic diseases may pose important clinical problems for the MM patients. Therefore, a catalogue of these problems is important so that physicians are able to consider, identify and address them promptly.

  12. Management of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM)

    National Research Council Canada - National Science Library

    Kyle, Robert A; Buadi, Francis; Rajkumar, S Vincent

    2011-01-01

    .... Risk factors for progression include the size of the serum M protein, the type of serum M protein, the number of plasma cells in the bone marrow, and the serum free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM...

  13. Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints.

    Science.gov (United States)

    Ai, Minrong; Cui, Yajun; Sy, Man-Sun; Lee, David M; Zhang, Ling Xiu; Larson, Katherine M; Kurek, Kyle C; Jay, Gregory D; Warman, Matthew L

    2015-01-01

    Lubricin, encoded by the gene PRG4, is the principal lubricant in articulating joints. We immunized mice genetically deficient for lubricin (Prg4-/-) with purified human lubricin, and generated several mAbs. We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), who genetically lack this protein. The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. Lubricin epitopes in blood do not represent degradation fragments from synovial fluid. Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid.

  14. Anti-lubricin monoclonal antibodies created using lubricin-knockout mice immunodetect lubricin in several species and in patients with healthy and diseased joints.

    Directory of Open Access Journals (Sweden)

    Minrong Ai

    Full Text Available Lubricin, encoded by the gene PRG4, is the principal lubricant in articulating joints. We immunized mice genetically deficient for lubricin (Prg4-/- with purified human lubricin, and generated several mAbs. We determined each mAb's binding epitope, sensitivity, and specificity using biologic samples and recombinant lubricin sub-domains, and we also developed a competition ELISA assay to measure lubricin in synovial fluid and blood. We found the mAbs all recognized epitopes containing O-linked oligosaccharides conjugated to the peptide motif KEPAPTTT. By western blot, the mAbs detected lubricin in 1 μl of synovial fluid from several animal species, including human. The mAbs were specific for lubricin since they did not cross-react with other synovial fluid constituents from patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP, who genetically lack this protein. The competition ELISA detected lubricin in blood samples from healthy individuals but not from patients with CACP, indicating blood can be used in a diagnostic test for patients suspected of having CACP. Lubricin epitopes in blood do not represent degradation fragments from synovial fluid. Therefore, although blood lubricin levels did not differentiate patients with inflammatory joint disease from healthy controls, epitope-specific anti-lubricin mAbs could be useful for monitoring disease activity in synovial fluid.

  15. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  16. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  17. Detection of kappa and lambda light chain monoclonal proteins in human serum: automated immunoassay versus immunofixation electrophoresis.

    Science.gov (United States)

    Jaskowski, Troy D; Litwin, Christine M; Hill, Harry R

    2006-02-01

    Recently, turbidimetric immunoassays for detecting and quantifying kappa and lambda free light chains (FLC) have become available and are promoted as being more sensitive than immunofixation electrophoresis (IFE) in detecting FLC monoclonal proteins. In this study, we assessed the ability of these turbidimetric assays to detect serum monoclonal proteins involving both free and heavy-chain-bound kappa and lambda light chains compared to standard immunofixation electrophoresis. Sera demonstrating a restricted band of protein migration (other than a definite M spike) by serum protein electrophoresis (SPE), which may represent early monoclonal proteins, were also examined. When compared to IFE, percent agreement, sensitivity, and specificity for the kappa-FLC and lambda-FLC were 94.6, 72.9, and 99.5% and 98.5, 91.4, and 99.7%, respectively, in detecting monoclonal proteins involving free and heavy-chain-bound light chains. The majority of sera (73.7%) demonstrating a restricted band of protein migration on SPE demonstrated abnormal IFE patterns suggestive of multiple myeloma or monoclonal gammopathy of unknown significance, but gave normal kappa/lambda FLC ratios using the turbidimetric immunoassays. In conclusion, the kappa and lambda FLC assays are significantly less sensitive (72.9 to 91.4%) than IFE, but specific in detecting serum monoclonal proteins. Moreover, the kappa/lambda ratio has little value in routine screening since the majority of sera with abnormal IFE patterns had normal kappa/lambda FLC ratios.

  18. Distinct and shared three-dimensional chromosome organization patterns in lymphocytes, monoclonal gammopathy of undetermined significance and multiple myeloma.

    Science.gov (United States)

    Sathitruangsak, Chirawadee; Righolt, Christiaan H; Klewes, Ludger; Tung Chang, Doris; Kotb, Rami; Mai, Sabine

    2017-01-15

    The consistent appearance of specific chromosomal translocations in multiple myeloma has suggested that the positioning of chromosomes in the interphase nucleus might play a role in the occurrence of particular chromosomal rearrangements associated with malignant transformation. Using fluorescence in situ hybridization, we have determined the positions of selected chromosome pairs (18 and 19, 9 and 22, 4 and 14, 14 and 16, 11 and 14) in interphase nuclei of myeloma cells compared to normal lymphocytes of treatment-naïve patients. All chromosome pairs were arranged in a nonrandom pattern. Chromosomes commonly involved in myeloma-associated translocations (4 and 14, 14 and 16, 11 and 14) were found in close spatial proximity, and this is correlated with the occurrence of overlapping chromosome territories. The spatial distribution of chromosomes may increase the possibility of chromosomal translocations in multiple myeloma. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  19. Heterogeneity of monoclonal antibodies.

    Science.gov (United States)

    Liu, Hongcheng; Gaza-Bulseco, Georgeen; Faldu, Dinesh; Chumsae, Chris; Sun, Joanne

    2008-07-01

    Heterogeneity of monoclonal antibodies is common due to the various modifications introduced over the lifespan of the molecules from the point of synthesis to the point of complete clearance from the subjects. The vast number of modifications presents great challenge to the thorough characterization of the molecules. This article reviews the current knowledge of enzymatic and nonenzymatic modifications of monoclonal antibodies including the common ones such as incomplete disulfide bond formation, glycosylation, N-terminal pyroglutamine cyclization, C-terminal lysine processing, deamidation, isomerization, and oxidation, and less common ones such as modification of the N-terminal amino acids by maleuric acid and amidation of the C-terminal amino acid. In addition, noncovalent associations with other molecules, conformational diversity and aggregation of monoclonal antibodies are also discussed. Through a complete understanding of the heterogeneity of monoclonal antibodies, strategies can be employed to better identify the potential modifications and thoroughly characterize the molecules.

  20. Monoclonal antibody "gold rush".

    Science.gov (United States)

    Maggon, Krishan

    2007-01-01

    The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush.

  1. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.;

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  2. Aspectos morfológicos da infiltração da medula óssea por condições exibindo diferenciação plasmocitária e gamopatia monoclonal Morphological aspects of bone marrow infiltration by diseases characterized by plasma cell proliferation and monoclonal gamopathy

    Directory of Open Access Journals (Sweden)

    Victor P. Andrade

    2009-08-01

    Full Text Available As doenças linfoproliferativas com diferenciação plasmocitária e pico monoclonal são causas de dificuldade diagnóstica no estudo de espécimes de medula óssea. Conhecer os aspectos clínicos, morfológicos, imunofenotípicos e citogenéticos é fundamental para o diagnóstico correto. Descrevemos os aspectos práticos mais relevantes para a interpretação de biópsias de medula óssea frente às situações mais frequentes.Some lymphoproliferative diseases with plasma cell differentiation and monoclonal gammopathy are challenging to diagnose when dealing with bone marrow biopsies. Knowledge of clinical, morphological, phenotypic and cytogenetic aspects is crucial to establish the correct diagnosis. We describe practical relevant aspects that help in the interpretation of bone marrow biopsies in these situations.

  3. Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update; Bildgebung des multiplen Myeloms und verwandter monoklonaler Plasmazellerkrankungen. Ein Update

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Marc-Andre [Universitaetsklinikum, Heidelberg (Germany). Abt. Diagnostische und Interventionelle Radiologie; Delorme, Stefan [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Radiologie; Hillengass, Jens [Universitaetsklinikum, Heidelberg (Germany). Sektion Multiples Myelom

    2014-09-15

    Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

  4. A randomized study of the relative pharmacokinetics, pharmacodynamics, and safety of alirocumab, a fully human monoclonal antibody to PCSK9, after single subcutaneous administration at three different injection sites in healthy subjects.

    Science.gov (United States)

    Lunven, Catherine; Paehler, Tobias; Poitiers, Franck; Brunet, Aurélie; Rey, Jacques; Hanotin, Corinne; Sasiela, William J

    2014-12-01

    We investigated the relative pharmacokinetics, pharmacodynamics, and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab following injection at three different sites. Sixty healthy subjects (39 male, 21 female; age 20-45 years) were randomized to receive a single subcutaneous injection of alirocumab 75 mg via 1-mL prefilled pen into the abdomen, upper arm, or thigh (NCT01785329). Subjects were followed for 85 days ± 2 days following study drug administration. Pharmacokinetic (PK) parameters for the systemic exposure of alirocumab were calculated, and levels of free PCSK9 were assessed. Percentage changes from baseline in LDL-C were compared between injection site groups using linear mixed-effects models. Alirocumab concentration-time profiles were similar, and free PCSK9 levels were reduced to approximately zero between Day 3 and Day 4 postinjection in all groups. LDL-C levels reached nadir on Day 15 postinjection in all groups with mean percentage reductions of 48.4% (abdomen), 39.5% (upper arm), and 45.6% (thigh) at this time point. A similar effect on LDL-C levels was seen across the entire time course of the study at all three injection sites. Treatment-emergent adverse events were experienced by 8/20 (abdomen), 11/20 (upper arm), and 13/20 (thigh) subjects. There were 2 mild/transient injection site reactions. There were no serious adverse events. A single subcutaneous administration of alirocumab 75 mg via prefilled pen was well tolerated with similar pharmacokinetics and pharmacodynamics when injected into the abdomen, upper arm, or thigh. These results suggest that alirocumab can be interchangeably injected in the abdomen, upper arm, or thigh. © 2014 Sanofi and Regeneron Pharmaceuticals Inc. Cardiovascular Therapeutics published by John Wiley & Sons Ltd.

  5. Fragmentation of monoclonal antibodies

    Science.gov (United States)

    Vlasak, Josef

    2011-01-01

    Fragmentation is a degradation pathway ubiquitously observed in proteins despite the remarkable stability of peptide bond; proteins differ only by how much and where cleavage occurs. The goal of this review is to summarize reports regarding the non-enzymatic fragmentation of the peptide backbone of monoclonal antibodies (mAbs). The sites in the polypeptide chain susceptible to fragmentation are determined by a multitude of factors. Insights are provided on the intimate chemical mechanisms that can make some bonds prone to cleavage due to the presence of specific side-chains. In addition to primary structure, the secondary, tertiary and quaternary structures have a significant impact in modulating the distribution of cleavage sites by altering local flexibility, accessibility to solvent or bringing in close proximity side chains that are remote in sequence. This review focuses on cleavage sites observed in the constant regions of mAbs, with special emphasis on hinge fragmentation. The mechanisms responsible for backbone cleavage are strongly dependent on pH and can be catalyzed by metals or radicals. The distribution of cleavage sites are different under acidic compared to basic conditions, with fragmentation rates exhibiting a minimum in the pH range 5–6; therefore, the overall fragmentation pattern observed for a mAb is a complex result of structural and solvent conditions. A critical review of the techniques used to monitor fragmentation is also presented; usually a compromise has to be made between a highly sensitive method with good fragment separation and the capability to identify the cleavage site. The effect of fragmentation on the function of a mAb must be evaluated on a case-by-case basis depending on whether cleavage sites are observed in the variable or constant regions, and on the mechanism of action of the molecule. PMID:21487244

  6. Uses of monoclonal antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2013-04-09

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

  7. Detection of Campylobacter species using monoclonal antibodies

    Science.gov (United States)

    Young, Colin R.; Lee, Alice; Stanker, Larry H.

    1999-01-01

    A panel of species specific monoclonal antibodies were raised to Campylobacter coli, Campylobacter jejuni and Campylobacter lari. The isotypes, and cross-reactivity profiles of each monoclonal antibody against an extensive panel of micro- organisms, were determined.

  8. Change in relative mobility of M protein following neuraminidase treatment in patients with multiple myeloma and monoclonal gammopathy of undetermined significance.

    Science.gov (United States)

    Kurihara, Yuriko; Iijima, Shiro; Fukushima, Kouhei; Hosaka, Toshiaki; Shiba, Kiyoko

    2004-01-01

    The aim of this study was to clarify the relationship between the relative mobility of M protein in various disease states using cellulose acetate membrane electrophoresis. To examine the carbohydrate chain of the M protein, sera from patients with multiple myeloma (MM), various cancers, and benign disease were treated with neuraminidase. The relative mobility in benign disease and MM patient sera following neuraminidase treatment varied among individuals, while that of IgG M protein in sera from cancer patients was from 0.2 to 0.3. Thus, the relative mobility in cancer patients was narrower than in those with MM or benign disease.However, after neuraminidase treatment, there was no significant difference between relative mobility in cancer patient's sera and those in other disease patients.

  9. Immunophenotypic heterogeneity of multiple myeloma: influence on the biology and clinical course of the disease. Castellano-Leones (Spain) Cooperative Group for the Study of Monoclonal Gammopathies.

    Science.gov (United States)

    San Miguel, J F; González, M; Gascón, A; Moro, M J; Hernández, J M; Ortega, F; Jimenez, R; Guerras, L; Romero, M; Casanova, F

    1991-02-01

    In 112 untreated myeloma patients we have analysed the immunophenotype of plasma cells both by immunofluorescence (IF) and immunocytochemistry (APAAP). Both techniques yielded similar results pointing to an important degree of heterogeneity in antigenic expression not only between different patients but also within the same patient. The expression of CD38 and Han-PC1 antigens (Ags) was almost constant (greater than 90% positive cases), while CD9 was detected in 66% of the cases. On the other hand, less than one third of patients were positive for CD10, CD20 and HLA-DR and generally with a weak expression (less than 30% positive plasma cells). In occasional cases plasma cells were weakly positive for the myelomonocytic markers CD13 (9%), CD15 (25%) and CD14 (6%). The possibility that this heterogeneity might be the result of different stages of differentiation of the neoplastic clone is suggested both by the positive correlation in the expression of some of these antigens (CD10, CD9, CD20, HLA-DR) and by the relationship between CD10 and myeloid antigens with immature plasma cell morphology. Finally, the cALLA antigen does not seem to be of significant value in predicting survival. Moreover, none of the other markers explored showed a clear influence in the course of the disease, although the tendency towards a lower survival found for the CD20+ cases as well as the association of the expression of some antigens and advanced clinical stage, may warrant further studies in a larger series of patients.

  10. Healthy shiftwork, healthy shiftworks.

    Science.gov (United States)

    Kogi, K

    2001-12-01

    Reflecting diversifying shift systems, extensive effort is put into managing shiftwork and reducing safety and health risks. It is accepted that shiftworkers are exposed to particular risks inherent in their irregular work schedules. This raises the question of how and to what extent we can ensure healthy work life for shiftworkers. In answering the question, we need to identify effective measures to improve both shiftworking conditions and the health of shiftworkers. Based on recent experiences in managing shiftwork, we note three directions of such measures: (a) comprehensive action to avoid risk-enhancing conditions based on general guidelines, (b) risk control as to workload, worksite ergonomics and risk reduction, and (c) support for flexible and restful working life. International standards are obviously relevant to these three aspects. Our own experiences in applying a set of ergonomic checkpoints to plant maintenance shiftwork demonstrate the usefulness of focusing on flexible work schedules and on multiple job-related factors such as night workload, ergonomic environment, resting conditions and training. There is a strong need for participatory planning and implementation of multi-area improvements as well as for relying on flexible schedules and autonomic teamwork. We may conclude that healthy shiftwork and healthy shiftworkers are compatible with each other only when certain conditions are met. In achieving this end, we need to combine (a) comprehensive measures to improve work schedules and job life, (b) strict risk management and (c) locally adjusted participatory steps for continual improvement.

  11. Advances in monoclonal antibody application in myocarditis

    Institute of Scientific and Technical Information of China (English)

    Li-na HAN; Shuang HE; Yu-tang WANG; Li-ming YANG; Si-yu LIU; Ting ZHANG

    2013-01-01

    Monoclonal antibodies have become a part of daily preparation technologies in many laboratories.Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases,inflammatory diseases,cancer,and other immune-associated diseases.This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis,an inflammatory disease of the heart,could be a novel approach in the future.In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis,we,through a significant amount of literature research both domestic and abroad,developed a systematic elaboration of monoclonal antibodies,pathogenesis of myocarditis,and application of monoclonal antibodies in myocarditis.This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future.Under conventional therapy,myocarditis is typically associated with congestive heart failure as a progressive outcome,indicating the need for alternative therapeutic strategies to improve long-term results.Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis,we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above.However,several issues remain.The technology on howto make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues.If we are to further stimulate

  12. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J

    2006-09-01

    Multiple options are now available for the treatment of chronic lymphocytic leukemia. Over the last 10 years, monoclonal antibodies have become an integral part of the management of this disease. Alemtuzumab has received approval for use in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab has been investigated extensively in chronic lymphocytic leukemia both as a single agent and in combination with chemotherapy and other monoclonal antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the early phase of clinical development. This article will review the monoclonal antibodies more commonly used to treat chronic lymphocytic leukemia, the results obtained with monoclonal antibodies as single agents and in combination with chemotherapy, and other biological agents and newer compounds undergoing clinical trials.

  13. The application of Gadopentate-Dimeneglumin has no impact on progression free and overall survival as well as renal function in patients with monoclonal plasma cell disorders if general precautions are taken

    Energy Technology Data Exchange (ETDEWEB)

    Hillengass, J. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany); Stoll, J.; Wagner, B.; Goldschmidt, H. [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Zechmann, C.M. [Rinecker Proton Therapy Center, Munich (Germany); Kunz, C.; Heiss, C. [German Cancer Research Center Heidelberg, Department of Biostatistics, Heidelberg (Germany); Sumkauskaite, M. [University of Heidelberg, Department of Radiology, Heidelberg (Germany); Moehler, T.M. [InVentiv Health Clinical, Wiesbaden (Germany); Schlemmer, H.P.; Delorme, S. [German Cancer Research Center Heidelberg, Department of Radiology, Heidelberg (Germany)

    2014-10-31

    The current analysis investigated the prognostic significance of gadopentetate dimeglumine on survival and renal function in patients with monoclonal plasma cell disorders. In this study 263 patients who had received gadopentetate dimeglumine within a prospective trial investigating dynamic contrast-enhanced magnetic resonance imaging (MRI) were compared with 335 patients who had undergone routine, unenhanced MRI. We found no significant prognostic impact of the application of contrast agent on progression-free survival in patients with either monoclonal gammopathy of undetermined significance, smouldering or symptomatic myeloma and no significant prognostic impact on overall survival in patients with symptomatic myeloma. Since renal impairment is a frequent complication of myeloma, and decreased renal function is associated with a higher risk of complications in patients receiving contrast agents, we evaluated the impact of contrast agent on renal function after 1 year. In the present analysis the only significant adverse impact on kidney function occurred in symptomatic myeloma patients who already had impaired renal parameters at baseline. Here, the renal function did not recover during therapy, whereas it did so in patients with normal or only slightly impaired renal function. If general recommendations are adhered to, gadopentetate dimeglumine can be safely applied in patients with monoclonal plasma cell disease. (orig.)

  14. Healthy Water

    Science.gov (United States)

    ... Topics Newsroom, Features, & Announcements CDC at Work: Healthy Water Fast Facts WASH-related Observances Top Causes of Drinking ... Features, & Announcements Training & Education CDC at Work: Healthy Water Policy & Recommendations Fast Facts Index of Water-Related Topics By A- ...

  15. Healthy Eating

    Science.gov (United States)

    ... Under Control Nutrition Guide for Toddlers Healthy Food Shopping What Should Preschoolers Drink? Healthy Drinks for Kids ... to Eating Right Learning About Calories Smart Supermarket Shopping Go, Slow, and Whoa! A Quick Guide to ...

  16. Healthy Schools

    Science.gov (United States)

    ... Wellness Policy Opportunities to create and support a healthy school environment. More Whole School, Whole Community, Whole Child A collaborative approach to learning and health Healthy Schools School Nutrition Environment Childhood Nutrition Facts Energy Drinks Obesity Prevention Youth ...

  17. Testes laboratoriais para avaliação do componente monoclonal Laboratory tests for evaluating the M-component

    Directory of Open Access Journals (Sweden)

    Paula Virginia Bottini

    2007-03-01

    Full Text Available As gamopatias monoclonais resultam de hiperprodução de um único clone anormal de células plasmocitárias ou linfócitos B. O objetivo da avaliação laboratorial nas gamopatias é demonstrar a presença, a quantidade e o tipo de proteína anormal presente no soro e/ou na urina através do estudo do perfil protéico, quantificação das imunoglobulinas e cadeias leves e avaliação da proteinúria. Este artigo descreve as principais técnicas laboratoriais disponíveis, bem como suas indicações e limitações.Monoclonal gammopathies result from an overproduction of a single abnormal clone of a plasma cell or B lymphocyte. The purpose of the laboratory protocols in these situations is to demonstrate the presence, the characterization and the concentration of an abnormal protein detected in serum and/or urine samples. The laboratory investigation is based on the electrophoretic protein profile, quantification of immunoglobulins, free light chains and proteinuria. This paper describes the major available laboratory methods as well their indications and limitations.

  18. Sensitivity of whole-body CT and MRI versus projection radiography in the detection of osteolyses in patients with monoclonal plasma cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Maya B., E-mail: m.mueller-wolf@dkfz.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Department of Radiology, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Murray, Fritz, E-mail: fritz.murray@hotmail.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Kilk, Kerstin, E-mail: k_fechtner@hotmail.com [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Hillengass, Jens, E-mail: jens.hillengass@med.uni-heidelberg.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Delorme, Stefan, E-mail: s.delorme@dkfz-heidelberg.de [Department of Radiology, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Heiss, Christiane, E-mail: c.heiss@dkfz-heidelberg.de [Department of Biostatistics, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Neben, Kai, E-mail: k.neben@klinikum-mittelbaden.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Goldschmidt, Hartmut, E-mail: hartmut.goldschmidt@med.uni-heidelberg.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg and National Center for Tumour Diseases, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kauczor, Hans-Ulrich, E-mail: hu.kauczor@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); and others

    2014-07-15

    Purpose: To compare sensitivity of whole-body Computed Tomography (wb-CT) and whole-body Magnetic Resonance Imaging (wb-MRI) with Projection Radiography (PR) regarding each method's ability to detect osteolyses in patients with monoclonal plasma cell disease. Patients and methods: The bone status of 171 patients was evaluated. All patients presented with multiple myeloma (MM) of all stages, monoclonal gammopathy of unknown significance (MGUS) or solitary plasmacytoma. Two groups were formed. Group A consisted of 52 patients (26 females, 26 males) with an average age of 62 years (range, 45–89 years) who received, both, PR and wb-CT as part of their diagnostic work-up. Group B comprised 119 patients (58 females, 61 males) averaging 57 years of age (range, 20–80 years) who received, both, PR and wb-MRI. Two experienced radiologists were blinded regarding the disease status and assessed the number and location of osteolyses in consensus. A distinction was made between axial and extra-axial lesions. Results: In group A, wb-CT revealed osteolyses in 12 patients (23%) that were not detected in PR. CT was superior in detecting lesions in patients with osteopenia and osteoporosis. Compared with PR, wb-CT was significantly more sensitive in detecting osteolyses than PR (p < 0.001). This was particularly true for axial lesions. Additionally, CT revealed clinically relevant incidental findings in 33 patients (63%). In group B, wb-MRI revealed lesions in 19 patients (16%) that were not detected in PR. All lesions detected by PR were also detected by wb-MRI and wb-CT. Wb-MRI and wb-CT are each superior to PR in detecting axial lesions. Conclusion: Wb-CT can detect 23% more focal lesions than PR, especially in the axial skeleton. Therefore, this imaging method should be preferred over PR in the diagnostic work-up and staging of patients with monoclonal plasma cell disease.

  19. Production and Screening of Monoclonal Peptide Antibodies.

    Science.gov (United States)

    Trier, Nicole Hartwig; Mortensen, Anne; Schiolborg, Annette; Friis, Tina

    2015-01-01

    Hybridoma technology is a remarkable and indispensable tool for generating high-quality monoclonal antibodies. Hybridoma-derived monoclonal antibodies not only serve as powerful research and diagnostic reagents, but have also emerged as the most rapidly expanding class of therapeutic biologicals. In this chapter, an overview of hybridoma technology and the laboratory procedures used routinely for hybridoma production and antibody screening are presented, including characterization of peptide antibodies.

  20. A monoclonal antibody against leptin.

    Science.gov (United States)

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin.

  1. Pharmacokinetics interactions of monoclonal antibodies.

    Science.gov (United States)

    Ferri, Nicola; Bellosta, Stefano; Baldessin, Ludovico; Boccia, Donatella; Racagni, Giorgi; Corsini, Alberto

    2016-09-01

    The clearance of therapeutic monoclonal antibodies (mAbs) typically does not involve cytochrome P450 (CYP450)-mediated metabolism or interaction with cell membrane transporters, therefore the pharmacokinetics interactions of mAbs and small molecule drugs are limited. However, a drug may affect the clearance of mAbs through the modulation of immune response (e.g., methotrexate reduces the clearance of infliximab, adalimumab, and golimumab, possibly due to methotrexate's inhibitory effect on the formation of antibodies against the mAbs). In addition, mAbs that are cytokine modulators may modify the metabolism of drugs through their effects on P450 enzymes expression. For example, cytokine modulators such as tocilizumab (anti-IL-6 receptor antibody) may reverse the "inhibitory" effect of IL-6 on CYP substrates, resulting in a "normalization" of CYP activities. Finally, a drug may alter the clearance of mAbs by either increasing or reducing the levels of expression of targets of mAbs on the cell surface. For instance, statins and fibrates induce PCSK9 expression and therefore increase cellular uptake and clearance of alirocumab and evolocumab, anti-PCSK9 antibodies. In the present review, we will provide an overview on the pharmacokinetics properties of mAbs as related to the most relevant examples of mAbs-small molecule drug interaction.

  2. Monoclonal anti-elastin antibody labelled with technetium-99m

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Marcia B.N. de; Silva, Claudia R. da; Araujo, Adriano C. de; Bernardo Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Instituto de Biologia Roberto Alcantara Gomes. Lab. de Radiofarmacia; Porto, Luis Cristovao M.S.; Gutfilen, Bianca [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Instituto de Biologia Roberto Alcantara Gomes; Souza, J.E.Q. [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil). Centro de Pesquisa Basica; Frier, Malcolm [University Hospital, Nottingham (United Kingdom). Dept. of Medical Physics

    1999-11-01

    Technetium-99m ({sup 99m} Tc) is widely employed in nuclear medicine due to its desirable physical, chemical and biological properties. Moreover, it is easily available and normally is inexpensive. A reducing agent is necessary to label cells and molecules with {sup 99m} Tc and stannous chloride (Sn C L{sub 2}) is usually employed. Elastin is the functional protein component of the elastic fiber and it is related with some diseases such as arteriosclerosis, pulmonary emphysema and others. The present study refers to the preparation of the {sup 99m} Tc labeled monoclonal anti-elastin antibody. The monoclonal antibody was incubated with an excess of 2-iminothiolane. The free thiol groups created, were capable of binding with the reduced technetium. Labeling was an exchange reaction with {sup 99m} Tc-glucoheptonate. The labeled preparation was left at 4 deg C for one hour. Then, it was passed through a Sephadex G50 column. Various fractions were collected and counted. A peak corresponding to the radiolabeled antibody was obtained. Stability studies of the labelled anti-elastin were performed at 0,3 6, 24 hours, at both 4 deg C or room temperature. The biodistribution pattern of the {sup 99m} Tc-anti-elastin was studied in healthy male Swiss mice. The immunoreactivity was also determined. An useful labeled-anti-elastin was obtained to future immunoscintigraphic investigations. (author) 4 refs., 7 figs., 6 tabs.

  3. A high-affinity human monoclonal IgM antibody reacting with multiple strains of Mycoplasma hominis

    DEFF Research Database (Denmark)

    Moller, SA; Birkelund, Svend; Borrebaeck, CA

    1990-01-01

    Human monoclonal antibodies were produced against Mycoplasma hominis by in vitro immunization of peripheral blood lymphocytes from a healthy seropositive donor using low amounts of antigen (5 ng/ml). The immune B lymphocytes were subsequently immortalized by Epstein-Barr virus transformation...

  4. Non-CLL-like monoclonal B-Cell lymphocytosis in the general population: Prevalence and phenotypic/genetic characteristics

    NARCIS (Netherlands)

    W.G. Nieto (Wendy); C. Teodosio (Cristina); A. López (Antonio); A. Rodríguez-Caballero (Arancha); A. Romero (Alfonso); P. Bárcena (Paloma); M.L. Gutierrez; A.W. Langerak (Anton); P. Fernandez-Navarro (Paulino); A. Orfao; J. Almeida (Julia); A.O.M.C.C.S. Santa Marta de Tormes; B.H.P.C.S. Garrido Sur; C.L.M.T.C.S. Ledesma; C.R.J.M.C.S. Alba de Tormes; C.L.R.C.S.F. Villalobos; D.V.P.J.C.S. Peñaranda; F.E.E.C.S. Pizarrales-Vidal; G.R.B.L.C.S. La Alberca; G.S.F.C.S. Periurbana Norte; G.M.J.C.S. Guijuelo; G.M.J.M.C.S. Vitigudino; J.R.M.J.C.S. Garrido Norte; J.C.T.B.C.S. Elena Ginel Diez; M.P.M.C.S. Fuentes de Oñoro; M.L.J.C.S. San Juan; M.D.M.P.C.S. Miguel Armijo; S.A.B.C.S. Aldeadavila de La Ribera; S.P.R.C.S. San Jose

    2010-01-01

    textabstractBackground: Monoclonal B-cell lymphocytosis (MBL) indicates <5 × 109peripheral blood (PB) clonal B-cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells - CLL-like MBL - but little is known about

  5. Non-CLL-like monoclonal B-Cell lymphocytosis in the general population: Prevalence and phenotypic/genetic characteristics

    NARCIS (Netherlands)

    W.G. Nieto (Wendy); C. Teodosio (Cristina); A. López (Antonio); A. Rodríguez-Caballero (Arancha); A. Romero (Alfonso); P. Bárcena (Paloma); M.L. Gutierrez; A.W. Langerak (Ton); P. Fernandez-Navarro (Paulino); A. Orfao; J. Almeida (Julia); A.O.M.C.C.S. Santa Marta de Tormes; B.H.P.C.S. Garrido Sur; C.L.M.T.C.S. Ledesma; C.R.J.M.C.S. Alba de Tormes; C.L.R.C.S.F. Villalobos; D.V.P.J.C.S. Peñaranda; F.E.E.C.S. Pizarrales-Vidal; G.R.B.L.C.S. La Alberca; G.S.F.C.S. Periurbana Norte; G.M.J.C.S. Guijuelo; G.M.J.M.C.S. Vitigudino; J.R.M.J.C.S. Garrido Norte; J.C.T.B.C.S. Elena Ginel Diez; M.P.M.C.S. Fuentes de Oñoro; M.L.J.C.S. San Juan; M.D.M.P.C.S. Miguel Armijo; S.A.B.C.S. Aldeadavila de La Ribera; S.P.R.C.S. San Jose

    2010-01-01

    textabstractBackground: Monoclonal B-cell lymphocytosis (MBL) indicates <5 × 109peripheral blood (PB) clonal B-cells/L in healthy individuals. In most cases, MBL cells show similar phenotypic/genetic features to chronic lymphocytic leukemia cells - CLL-like MBL - but little is known about non-CLL-li

  6. Healthy Eyes

    Science.gov (United States)

    ... los Ojos Cómo hablarle a su oculista Healthy Eyes Having a comprehensive dilated eye exam is one ... or contact lenses. What is a comprehensive dilated eye exam? A comprehensive dilated eye exam is a ...

  7. Healthy Ageing

    NARCIS (Netherlands)

    Dr. C.P. van der Schans

    2015-01-01

    Presentatie gehouden bij de bijeenkomst voor het Regionaal Genootschap Fysiotherapie Het Noorden op 10 februari te Marum, over het belang van fysieke activiteit voor healthy ageing en de rol van de fysiotherapeut hierin

  8. A single-arm, open-label, phase 2 clinical trial evaluating disease response following treatment with BI-505, a human anti-intercellular adhesion molecule-1 monoclonal antibody, in patients with smoldering multiple myeloma

    Science.gov (United States)

    Wichert, Stina; Juliusson, Gunnar; Johansson, Åsa; Sonesson, Elisabeth; Teige, Ingrid; Wickenberg, Anna Teige; Frendeus, Björn; Korsgren, Magnus; Hansson, Markus

    2017-01-01

    Background Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects. BI-505 was well tolerated in an earlier phase 1 trial. Methods and findings In this phase 2 trial the effects of BI-505 in patients with SMM were studied. Four patients were enrolled and three of them completed the first cycle of treatment defined as 5 doses of BI-505, a total of 43 mg/kg BW, over a 7-week period. In the three evaluable patients, BI-505 showed a benign safety profile. None of the patients achieved a response as defined per protocol. EudraCT number: 2012-004884-29. Conclusions The study was conducted to assess the efficacy, safety and pharmacodynamics of BI-505 in patients with SMM. BI-505 showed no clinically relevant efficacy on disease activity in these patients with SMM, even if well tolerated. Trial registration ClinicalTrials.gov Identifier: NCT01838369. PMID:28158311

  9. Healthy Places

    Centers for Disease Control (CDC) Podcasts

    2007-04-10

    Every person has a stake in environmental public health. As the environment deteriorates, so does the physical and mental health of the people within it. Healthy places are those designed and built to improve the quality of life for all people who live, work, worship, learn, and play within their borders -- where every person is free to make choices amid a variety of healthy, available, accessible, and affordable options. The CDC recognizes significant health issues and places that are vital in developing the Healthy Places program and provides examples in this report.  Created: 4/10/2007 by CDC National Center for Environmental Health.   Date Released: 4/13/2007.

  10. Human Monoclonal Antibodies as a Countermeasure Against Botulinum Toxins

    Science.gov (United States)

    2012-11-30

    REPORT Human monoclonal antibodies as a countermeasure against Botulinum toxins 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: In this report, we...Prescribed by ANSI Std. Z39.18 - 31-Aug-2012 Human monoclonal antibodies as a countermeasure against Botulinum toxins Report Title ABSTRACT In this report...DTRA Final Report: Human monoclonal antibodies as a countermeasure against Botulinum toxins   Page 1 of 22 DTRA Final Report: Human monoclonal

  11. Healthy Learning.

    Science.gov (United States)

    Kennedy, Mike

    2003-01-01

    Offers ten suggestions for schools and universities to help maintain a healthy indoor environment: proper flooring, sanitary washrooms, consistent maintenance, indoor air quality, preventing mold, daylighting, good acoustics, avoiding volatile organic compounds (VOCs), ergonomic furniture, and well-maintained roofs. (EV)

  12. Healthy Dragon

    Institute of Scientific and Technical Information of China (English)

    孙继山

    2005-01-01

    The Chinese economic dragon is healthy and dynamic. The dragorthead,Shanghai, is developing at a pace never before seen in world history, The dragon's body is also doing well, not least because there is tremendous competition across the country. Thus, four cities along the central Yangtze River Region are trying to strengthen their competitiveness.

  13. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia.

  14. Monoclonal antibody technologies and rapid detection assays

    Science.gov (United States)

    Novel methodologies and screening strategies will be outlined on the use of hybridoma technology for the selection of antigen specific monoclonal antibodies. The development of immunoassays used for diagnostic detection of prions and bacterial toxins will be discussed and examples provided demonstr...

  15. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  16. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    1989-01-01

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia. Antibod

  17. 单克隆抗体治疗免疫性周围神经病进展%Monoclonal antibodies for diseases of the peripheral nervous system

    Institute of Scientific and Technical Information of China (English)

    孙广锋; 余建华

    2011-01-01

    Conventional treatment options, corticosteroids, intravenous immunoglobulin, or plasma exchange,often fail to treat dysimmune neuropathies, such as chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and monoclonal gammopathy. Currently, several monoclonal antibodies (MAbs) have been tested in the therapy for diseases of the peripheral nervous system(PNS). Rituximab, is the most widely used and a promising MAb for the treatment of dysimmune neuropathies. The efficacy of alemtuzumab and bevacizumab on treating various forms of dysimmune neuropathies is currently under investigation, especially for disorders that are resistant to conventional treatment options.%免疫性周围神经病如慢性炎症性脱髓鞘性多发性神经病(CIDP)、多病灶运动神经病(MMN)等常规方法治疗疗效有时较差和毒性较大.目前几种单克隆抗体(MAbs)已经试用于免疫性周围神经病的治疗.小范围研究或在单个病例,以建立未来的方向周围神经系统疾病治疗的未来方向.利妥昔单抗,是治疗免疫性神经病应用最广泛和最有前景的MAb,阿仑单抗和贝伐单抗等也试用于治疗各种免疫异常的神经病变.对有些难治性周围神经病,单克隆抗体是一种新的安全有效的治疗方法.

  18. Isolation of highly active monoclonal antibodies against multiresistant gram-positive bacteria.

    Directory of Open Access Journals (Sweden)

    Friederike S Rossmann

    Full Text Available Multiresistant nosocomial pathogens often cause life-threatening infections that are sometimes untreatable with currently available antibiotics. Staphylococci and enterococci are the predominant Gram-positive species associated with hospital-acquired infections. These infections often lead to extended hospital stay and excess mortality. In this study, a panel of fully human monoclonal antibodies was isolated from a healthy individual by selection of B-cells producing antibodies with high opsonic killing against E. faecalis 12030. Variable domains (VH and VL of these immunoglobulin genes were amplified by PCR and cloned into an eukaryotic expression vector containing the constant domains of a human IgG1 molecule and the human lambda constant domain. These constructs were transfected into CHO cells and culture supernatants were collected and tested by opsonophagocytic assay against E. faecalis and S. aureus strains (including MRSA. At concentrations of 600 pg/ml, opsonic killing was between 40% and 70% against all strains tested. Monoclonal antibodies were also evaluated in a mouse sepsis model (using S. aureus LAC and E. faecium, a mouse peritonitis model (using S. aureus Newman and LAC and a rat endocarditis model (using E. faecalis 12030 and were shown to provide protection in all models at a concentration of 4 μg/kg per animal. Here we present a method to produce fully human IgG1 monoclonal antibodies that are opsonic in vitro and protective in vivo against several multiresistant Gram-positive bacteria. The monoclonal antibodies presented in this study are significantly more effective compared to another monoclonal antibody currently in clinical trials.

  19. Monoclonal Antibodies to Plant Growth Regulators

    Science.gov (United States)

    Eberle, Joachim; Arnscheidt, Angelika; Klix, Dieter; Weiler, Elmar W.

    1986-01-01

    Four high affinity monoclonal antibodies, which recognize two plant growth regulators from the cytokinin group, namely trans-zeatin riboside and dihydrozeatin riboside and their derivatives are reported. Six hybridomas were produced from three independent fusions of Balb/c spleen cells with P3-NS1-Ag 4-1 (abbreviated NS1) or X63-Ag 8.653 (X63) myeloma cells. The mice had been hyperimmunized with zeatin riboside-bovine serum albumin conjugate or dihydrozeatin riboside-bovine serum albumin conjugate for 3 months. The hybridomas secrete antibodies of the IgG 1 or IgG 2b subclass and allow the detection of femtomole amounts of the free cytokinins, their ribosides, and ribotides in plant extracts. The use of these monoclonals in radio- and enzyme-linked immunosorbent assay is also discussed. PMID:16664848

  20. Recent developments in monoclonal antibody radiolabeling techniques

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.; Mease, R.C.

    1989-01-01

    Monoclonal antibodies (MAbs) have shown the potential to serve as selective carriers of radionuclides to specific in vivo antigens. Accordingly, there has been an intense surge of research activity in an effort to develop and evaluate MAb-based radiopharmaceuticals for tumor imaging (radioimmunoscintigraphy) and therapy (radioimmunotherapy), as well as for diagnosing nonmalignant diseases. A number of problems have recently been identified, related to the MAbs themselves and to radiolabeling techniques, that comprise both the selectivity and the specificity of the in vivo distribution of radiolabeled MAbs. This paper will address some of these issues and primarily discuss recent developments in the techniques for radiolabeling monoclonal antibodies that may help resolve problems related to the poor in vivo stability of the radiolabel and may thus produce improved biodistribution. Even though many issues are identical with therapeutic radionuclides, the discussion will focus mainly on radioimmunoscintigraphic labels. 78 refs., 6 tabs.

  1. Polyclonal and monoclonal antibodies in clinic.

    Science.gov (United States)

    Wootla, Bharath; Denic, Aleksandar; Rodriguez, Moses

    2014-01-01

    Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino-acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. Naturally occurring antibodies protect the organism against harmful pathogens, viruses and infections. In addition, almost any organic chemical induces antibody production of antibodies that would bind specifically to the chemical. These antibodies are often produced from multiple B cell clones and referred to as polyclonal antibodies. In recent years, scientists have exploited the highly evolved machinery of the immune system to produce structurally and functionally complex molecules such as antibodies from a single B clone, heralding the era of monoclonal antibodies. Most of the antibodies currently in the clinic, target components of the immune system, are not curative and seek to alleviate symptoms rather than cure disease. Our group used a novel strategy to identify reparative human monoclonal antibodies distinct from conventional antibodies. In this chapter, we discuss the therapeutic relevance of both polyclonal and monoclonal antibodies in clinic.

  2. Application of monoclonal antibody panels in the virological and epidemiological review of poliomyelitis in Poland, 1981-1990.

    OpenAIRE

    Jarzabek, Z.; Zabicka, J.; John, A.; Howlett, J.; Dunn, G.; Wood, D. J.

    1992-01-01

    Monoclonal antibody panels developed to differentiate vaccine-derived and wild-type strains of polio-viruses were applied to isolates from cases of paralytic poliomyelitis, non-paralytic poliomyelitis, and healthy excreters of poliovirus from Poland. All isolates from poliomyelitis cases were shown to be vaccine-derived, as were most other strains. However, two strains associated with meningitis had wild-type antigenic phenotypes and, as shown by partial genomic sequencing, wild-type genotype...

  3. Assay for the specificity of monoclonal antibodies in crossed immunoelectrophoresis

    DEFF Research Database (Denmark)

    Skjødt, K; Schou, C; Koch, C

    1984-01-01

    A method is described based on crossed immunoelectrophoresis of a complex antigen mixture in agarose gel followed by incubation of the gel with the monoclonal antibody. The bound monoclonal antibody is detected by the use of a secondary enzyme-labelled antibody. Using this technique we have been...... I molecules. In other experiments using the same technique we demonstrated the reaction of a monoclonal antibody specific for chicken Ig light chains. Udgivelsesdato: 1984-Aug-3...

  4. ON THE NOTION OF SYNERGY OF MONOCLONAL ANTIBODIES AS DRUGS

    Directory of Open Access Journals (Sweden)

    Michael Sela

    2013-08-01

    Full Text Available History of developing synergy between monoclonal antibodies, anti-tumor activity of monoclonal antibodies against tyrosine-kinases receptors EGFR/ErbB-1 and HER2/ErbB-2 as well as growth factor VEGF in various combinations are considered in the article. There were proposed hypotheses about potential molecular mechanisms underlay synergy between monoclonal antibodies (for homo- and hetero combinations of antibodies appropriately specific for antigenic determinants on the same or different receptors. Future trends in researches necessary to deeper understanding causes of this phenomenon and perspectives for practical application of monoclonal antibodies acted synergistically as immunotherapeutic drugs for human tumors treatment are reviewed.

  5. The Role of Monoclonal Antibodies in the Management of Leukemia

    Science.gov (United States)

    Al-Ameri, Ali; Cherry, Mohamad; Al-Kali, Aref; Ferrajoli, Alessandra

    2010-01-01

    This article will review the monoclonal antibodies more commonly used in leukemias. In the last three decades, scientists have made considerable progress understanding the structure and the functions of various surface antigens, such as CD20, CD33. The introduction of rituximab, an anti CD20 monoclonal antibody, had a great impact in the treatment of lymphoproliferative disorders. Gemtuzumab, an anti CD 33 conjugated monoclonal antibody has activity in acute mylegenous leukemia (AML). As this field is undergoing a rapid growth, the years will see an increasing use of monoclonal antibodies in hematological malignancies.

  6. The Role of Monoclonal Antibodies in the Management of Leukemia

    Directory of Open Access Journals (Sweden)

    Mohamad Cherry

    2010-10-01

    Full Text Available This article will review the monoclonal antibodies more commonly used in leukemias. In the last three decades, scientists have made considerable progress understanding the structure and the functions of various surface antigens, such as CD20, CD33. The introduction of rituximab, an anti CD20 monoclonal antibody, had a great impact in the treatment of lymphoproliferative disorders. Gemtuzumab, an anti CD 33 conjugated monoclonal antibody has activity in acute mylegenous leukemia (AML. As this field is undergoing a rapid growth, the years will see an increasing use of monoclonal antibodies in hematological malignancies.

  7. Healthy Water Healthy People Field Monitoring Guide

    Science.gov (United States)

    Project WET Foundation, 2003

    2003-01-01

    This 100-page manual serves as a technical reference for the "Healthy Water, Healthy People Water Quality Educators Guide" and the "Healthy Water Healthy People Testing Kits". Yielding in-depth information about ten water quality parameters, it answers questions about water quality testing using technical overviews, data interpretation guidelines,…

  8. [ICO-10 monoclonal antibodies to the Thy-1 antigen].

    Science.gov (United States)

    Korotkova, O V; Baryshnikov, A Iu; Tupitsyn, N N; Chimishkian, K L; Kostrykina, V N

    1989-01-01

    Mouse monoclonal antibodies (MAB) ICO-10 to Thy-1 antigen were obtained. MAB ICO-10 reacted in indirect immunofluorescence test with 5.7 +/- 0.8% human thymocytes. Antibodies did not react with granulocytes, monocytes, T- and non-T cells from peripheral blood, and with marrow cells of healthy donors. MAB ICO-10 reacted with blast cells from 25 of 53 patients with T-cell acute lymphoblastic leukemia (ALL), from 2 of 5 patients with B-cell ALL. This antigen was absent on blood and marrow cells from some patients with ALL, 80 patients with chronic lymphoid leukemia, 54 patients with chronic granulocytic leukemia at the stage of blastic crisis, 128 patients with acute nonlymphoblastic leukemia. Antibodies are specifically bound to thymocytes and spleen cells of Thy 1.1 and Thy 1.2 mice. MAB ICO-10 detect Thy-1 antigen expressed on human hematopoietic cells. MAB ICO-10 may be applied for human leukemia and lymphoma immune diagnosis.

  9. Production of Monoclonal Antibody against Human Nestin.

    Science.gov (United States)

    Hadavi, Reza; Zarnani, Amir Hassan; Ahmadvand, Negah; Mahmoudi, Ahmad Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Sadeghi, Mohammad-Reza; Soltanghoraee, Haleh; Akhondi, Mohammad Mehdi; Tarahomi, Majid; Jeddi-Tehrani, Mahmood; Rabbani, Hodjattallah

    2010-04-01

    We have employed a peptide-based antibody generation protocol for producing antibody against human nestin. Using a 12-mer synthetic peptide from repetitive region of human nestin protein devoid of any N- or O-glyco-sylation sequences, we generated a mouse monoclonal antibody capable of recognizing human, mouse, bovine, and rat nestin. A wide variety of nestin proteins ranging from 140-250 kDa was detected by this antibody. This antibody is highly specific and functional in applications such as ELISA, flow cytometry, immunocytochemistry, and Western blot assays.

  10. Monoclonal Idiotope Vaccine against Streptococcus pneumoniae Infection

    Science.gov (United States)

    McNamara, Mary K.; Ward, Ronald E.; Kohler, Heinz

    1984-12-01

    A monoclonal anti-idiotope antibody coupled to a carrier protein was used to immunize BALB/c mice against a lethal Streptococcus pneumoniae infection. Vaccinated mice developed a high titer of antibody to phosphorylcholine, which is known to protect against infection with Streptococcus pneumoniae. Measurement of the median lethal dose of the bacteria indicated that anti-idiotope immunization significantly increased the resistance of BALB/c mice to the bacterial challenge. Antibody to an idiotope can thus be used as an antigen substitute for the induction of protective immunity.

  11. Anaphylaxis to chemotherapy and monoclonal antibodies.

    Science.gov (United States)

    Castells, Mariana C

    2015-05-01

    Hypersensitivity reactions are increasingly prevalent, although underrecognized and underreported. Platins induce immunoglobulin E-mediated sensitization; taxenes and some monoclonal antibodies can induce reactions at first exposure. Severe hypersensitivity can preclude first-line therapy. Tryptase level at the time of a reaction is a useful diagnostic tool. Skin testing provides a specific diagnosis. Newer tests are promising diagnostic tools to help identify patients at risk before first exposure. Safe management includes rapid drug desensitization. This review provides information regarding the scope of hypersensitivity and anaphylactic reactions induced by chemotherapy and biological drugs, as well as diagnosis, management, and treatment options.

  12. Study on biodistribution of 131 iodine labeled monoclonal antibody D-D3 against pro-gastrin-releasing peptide(31-98) in healthy Kunming mice%抗ProGRP(31-98)单克隆抗体D-D3的131I标记及其体内生物学分布研究

    Institute of Scientific and Technical Information of China (English)

    陈传新; 石怡珍; 杨仪; 唐军; 刘增礼; 徐巧玲

    2011-01-01

    Objective To study the 131I labeling methods, stability, and biological distribution pattern of D-D3 antibody against pro-gastrin-releasing peptide 31-98(ProGRP(31-98) ). Methods The radioiodination of D-D3 antibody was performed using the chloramine-T method. The radiochemical purity was determined through thin-layer chromotography. 131I-D-D3 was injected into the healthy Kunming mice via a tail vein, and the % ID/g for various organs was obtained, and then, the biodistribution and pharmacokinetics of 131 I-D-D3 antibody in healthy Kunming mice were studied. Results The 131 I-D-D3 labeling rate was (86.56 ± 3.8) %. The radiochemical purity of 131 I-D-D3 was (99.27 ± 0. 6)%. After 48 h incubating in 37 ℃ water bath, the radiochemical purity was (88.38 ± 0.4)%. While being mixed 24 h with healthy human serum, the radiochemical purity was still more than (64.43 ± 0.7)%. The metabolism of 131I-D-D3 in healthy Kunming mice was consistent with a two-compartment model with first-order absorption, T1/2α and T1/2β was 0.25,37.89 h, respectively. Conclusion The labeling efficiency and radiochemical purity of 131 I-D-D-D3 are high and stable. 131I-D-D3 is a promising radioimmunoimaging reagent for small cell lung cancer(SCLC).%目的 探讨抗胃泌素释放肽前体(ProGRP)(31-98)单克隆抗体D-D3的131I标记方法 及其在健康昆明小鼠体内的生物学分布规律与特点.方法 采用氯胺-T法用131I标记单克隆抗体D-D3,利用纸层析法测定其标记率、放化纯度和稳定性.取健康昆明小鼠50只,随机分为10组,每组5只,自昆明小鼠尾静脉注射131I-D-D3 1.48 kBq/100 μL(4 μCi/100 μL),各组小鼠分别于注射后5、15、30 min及1、2、4、8、12、24、48 h处死,取血液、心脏、肝脏、脾脏、肺脏、肾脏、胃、小肠、骨骼(右下肢)、肌肉(右下肢)和脑组织,称质量(g)后测放射性计数(cpm),计算各脏器组织的每克组织百分注射剂量率(%ID

  13. Bellagio report on Healthy agriculture, healthy nutrition, healthy people⋆

    OpenAIRE

    Simopoulos Artemis P.; Bourne Peter G.; Faergeman Ole

    2013-01-01

    The Bellagio Report on Healthy agriculture, healthy nutrition, healthy people is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October–2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that m...

  14. Emerging monoclonal antibodies against Clostridium difficile infection.

    Science.gov (United States)

    Péchiné, Séverine; Janoir, Claire; Collignon, Anne

    2017-04-01

    Clostridium difficile infections are characterized by a high recurrence rate despite antibiotic treatments and there is an urgent need to develop new treatments such as fecal transplantation and immonotherapy. Besides active immunotherapy with vaccines, passive immunotherapy has shown promise, especially with monoclonal antibodies. Areas covered: Herein, the authors review the different assays performed with monoclonal antibodies against C. difficile toxins and surface proteins to treat or prevent primary or recurrent episodes of C. difficile infection in animal models and in clinical trials as well. Notably, the authors lay emphasis on the phase III clinical trial (MODIFY II), which allowed bezlotoxumab to be approved by the Food and Drug Administration and the European Medicines Agency. They also review new strategies for producing single domain antibodies and nanobodies against C. difficile and new approaches to deliver them in the digestive tract. Expert opinion: Only two human Mabs against TcdA and TcdB have been tested alone or in combination in clinical trials. However, many animal model studies have provided rationale for the use of Mabs and nanobodies in C. difficile infection and pave the way for further clinical investigation.

  15. Aggregates in monoclonal antibody manufacturing processes.

    Science.gov (United States)

    Vázquez-Rey, María; Lang, Dietmar A

    2011-07-01

    Monoclonal antibodies have proved to be a highly successful class of therapeutic products. Large-scale manufacturing of pharmaceutical antibodies is a complex activity that requires considerable effort in both process and analytical development. If a therapeutic protein cannot be stabilized adequately, it will lose partially or totally its therapeutic properties or even cause immunogenic reactions thus potentially further endangering the patients' health. The phenomenon of protein aggregation is a common issue that compromises the quality, safety, and efficacy of antibodies and can happen at different steps of the manufacturing process, including fermentation, purification, final formulation, and storage. Aggregate levels in drug substance and final drug product are a key factor when assessing quality attributes of the molecule, since aggregation might impact biological activity of the biopharmaceutical. In this review it is analyzed how aggregates are formed during monoclonal antibody industrial production, why they have to be removed and the manufacturing process steps that are designed to either minimize or remove aggregates in the final product. Copyright © 2011 Wiley Periodicals, Inc.

  16. Kidney failure as an unusual initial presentation of biclonal gammopathy (IgD multiple myeloma associated with light chain disease: A case report

    Directory of Open Access Journals (Sweden)

    Rabrenović Violeta

    2015-01-01

    Full Text Available Introduction. Immunoglobulin D (IgD myeloma is a rare disease, about 2% of all myelomas, even rarer when accompanied with another multiple myeloma in biclonal gammopathy. We presented a case of biclonal gammopathy - associated manifestation of IgD myeloma and light chain disease in a patient who initially had renal failure. Case report. 37-year-old male approximately one month before hospitalization began to feel malaise and fatigue along with decreased urination. Laboratory analysis revealed azotemia. A dialysis catheter was placed and hemodialysis started. The patient was then admitted to our hospital for further tests and during admission, objective examination revealed pronounced paleness with hepatosplenomegaly and hypertension (170/95 mmHg. Laboratory analysis showed erythrocyte sedimentation rate 122 mm/h, expressed anemic syndrome (Hb 71 g/L and renal failure dialysis rank: creatinine 1,408 μmol/L, urea31.7 mmol/L. There was two M components in serum protein electrophoresis: IgD lambda and free light chain lambda. Proteinuria was nephrotic rank (5.4 g/24 h, whose electrophoresis revealed 2 M components - massive in α 2 fraction of 71%; 7% in the discrete β fraction, beta 2M /serum 110 mg/L, in urine 1.8 mg/L - extremely high; IgL kappa / lambda index 1 : 13 (reference value ratio 2 : 1. The findings pointed to double myeloma disease: IgD myeloma and Bence Jones lambda myeloma. Bone biopsy confirmed IgD myeloma lambda 100% infiltration medulla predominantly plasmablasts. The treatment continued with hemodialysis 3 times per week with chemotherapy protocol bortezomib, doxorubicin, dexamethasone. After 4 cycles of chemotherapy, there was a decrease of IgD, λ - light chains, reduction in proteinuria (1.03 g/24 h, so hemodialysis was reduced to once per week. Six months after treatment initiation the patient underwent autologous bone marrow transplantation. In a 2-year follow-up period double myeloma disease showed complete remission

  17. Immunochemical Characterization of Anti-Acetylcholinesterase Inhibitory Monoclonal Antibodies

    Science.gov (United States)

    1993-01-01

    formation. This conformation was first proposed using studies with monoclonal antibodies against a synthetic peptide mimicking the sequence of the...distinct antigenic determinants on dengue -2 virus using monoclonal antibodies, Am. J. Trop. Med. Hyg., 31 (1982) 548-555. 7 D. De la Hoz, B.P. Doctor

  18. Monoclonal Antibodies Specific for Hippurate Hydrolase of Campylobacter jejuni

    OpenAIRE

    Steele, Marina; Gyles, Carlton; Chan, Voon Loong; Odumeru, Joseph

    2002-01-01

    Eleven monoclonal antibodies raised against recombinant Campylobacter jejuni hippurate hydrolase were tested for binding to lysates from 19 C. jejuni strains, 12 other Campylobacter strains, and 21 non-Campylobacter strains. Several monoclonal antibodies bound to C. jejuni but not to other Campylobacter species and may be useful in a species-specific immunoassay.

  19. Inherited predisposition to CLL is detectable as subclinical monoclonal B-lymphocyte expansion.

    Science.gov (United States)

    Rawstron, Andy C; Yuille, Martin R; Fuller, Julie; Cullen, Matthew; Kennedy, Ben; Richards, Stephen J; Jack, Andrew S; Matutes, Estella; Catovsky, Daniel; Hillmen, Peter; Houlston, Richard S

    2002-10-01

    Monoclonal chronic lymphocytic leukemia (CLL)-phenotype cells are detectable in 3.5% of otherwise healthy persons using flow cytometric analysis of CD5/CD20/CD79b expression on CD19-gated B cells. To determine whether detection of such CLL-phenotype cells is indicative of an inherited predisposition, we examined 59 healthy, first-degree relatives of patients from 21 families with CLL. CLL-phenotype cells were detected in 8 of 59 (13.5%) relatives, representing a highly significant increase in risk (P =.00002). CLL-phenotype cell levels were stable with time and had the characteristics of indolent CLL. Indolent and aggressive clinical forms were found in family members, suggesting that initiation and proliferation involves distinct factors. The detection of CLL-phenotype cells provides a surrogate marker of carrier status, potentially facilitating gene identification through mapping in families and direct analysis of isolated CLL-phenotype cells.

  20. Treatment with anti-interferon-δ monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-δ receptor knockout mice

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.

    2001-01-01

    Neuroinflammation, neuronal degeneration, regeneration, monoclonal antibodies, multiple schlerosis......Neuroinflammation, neuronal degeneration, regeneration, monoclonal antibodies, multiple schlerosis...

  1. Induction and characterization of monoclonal anti-idiotypic antibodies reactive with idiotopes of canine parvovirus neutralizing monoclonal antibodies.

    NARCIS (Netherlands)

    G.F. Rimmelzwaan (Guus); J. van Es (Johan); G.A. Drost; F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1991-01-01

    textabstractMonoclonal anti-idiotypic (anti-Id) antibodies (Ab2) were generated against idiotypes (Id) of canine parvovirus (CPV) specific monoclonal antibodies (MoAbs). The binding of most of these anti-Id antibodies to their corresponding Id could be inhibited by antigen, thus classifying these an

  2. Novel monoclonal treatments in severe asthma

    DEFF Research Database (Denmark)

    Meteran, Howraman; Meteran, Hanieh; Porsbjerg, Celeste

    2017-01-01

    AIM: To provide a general overview of the current biological treatments and discuss their potential anti-asthmatic effects. DATA SOURCES: We reviewed articles in PubMed found using the search words "Asthma/therapy AND antibodies, monoclonal/therapeutic use AND cytokines." STUDY SELECTIONS: Only...... articles published in English since 2000 were considered. The search identified 29 studies; 8 additional studies were found by hand search, generating 37 studies. RESULTS: Of the 37 studies investigating biological treatments of asthma, 5 were on the effects of anti-IgE (omalizumab); 12 on anti-IL-5; 8...... TSLP, IL-9, and TNF-α lacked convincing effectiveness. CONCLUSION: Research on the biological treatment of asthma shows promising results. While anti-IgE (omalizumab) has been used in the treatment of asthma for some years, anti-IL-5 has recently been approved for use. The efficacy of results of other...

  3. Healthy Vision Tips

    Science.gov (United States)

    ... NEI for Kids > Healthy Vision Tips All About Vision About the Eye Ask a Scientist Video Series ... Links to More Information Optical Illusions Printables Healthy Vision Tips Healthy vision starts with you! Use these ...

  4. Healthy Lifestyle: Children's Health

    Science.gov (United States)

    Healthy Lifestyle Children's health You want your child to eat healthy foods, but do you know which nutrients ... 16, 2016 Original article: http://www.mayoclinic.org/healthy-lifestyle/childrens-health/in-depth/nutrition-for-kids/art- ...

  5. Keeping Your Voice Healthy

    Science.gov (United States)

    ... Find an ENT Doctor Near You Keeping Your Voice Healthy Keeping Your Voice Healthy Patient Health Information ... heavily voice-related. Key Steps for Keeping Your Voice Healthy Drink plenty of water. Moisture is good ...

  6. Healthy food trends -- kale

    Science.gov (United States)

    Healthy food trends - borecole; Healthy snacks - kale; Weight loss - kale; Healthy diet - kale; Wellness - kale ... drugs), you may need to limit vitamin K foods. Vitamin K can affect how these medicines work. ...

  7. Having a Healthy Pregnancy

    Science.gov (United States)

    ... Week of Healthy Breakfasts Shyness Having a Healthy Pregnancy KidsHealth > For Teens > Having a Healthy Pregnancy A ... or she can help you to get treatment. Pregnancy Discomforts Pregnancy can cause some uncomfortable side effects. ...

  8. Healthy Dining Hall Eating

    Science.gov (United States)

    ... A Week of Healthy Breakfasts Shyness Healthy Dining Hall Eating KidsHealth > For Teens > Healthy Dining Hall Eating ... likely to eat. previous continue Overcoming Common Dining Hall Mistakes Even the most attentive diners can still ...

  9. Healthy Sleep Habits

    Science.gov (United States)

    ... Sleep Apnea Testing CPAP Healthy Sleep Habits Healthy Sleep Habits Your behaviors during the day, and especially ... team at an AASM accredited sleep center . Quick Sleep Tips Follow these tips to establish healthy sleep ...

  10. Healthy food trends -- quinoa

    Science.gov (United States)

    Healthy food trends - goosefoot; Healthy snacks - quinoa; Weight loss - quinoa; Healthy diet - quinoa; Wellness - quinoa ... Quinoa is rich in protein . It has almost twice the amount of protein found in oats, and ...

  11. Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People

    OpenAIRE

    Ole Faergeman; Simopoulos, Artemis P.; Peter G. Bourne

    2013-01-01

    The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October–2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD’s) wo...

  12. Sub-Nanogram Detection of RDX Explosive by Monoclonal Antibodies.

    Science.gov (United States)

    Ulaeto, David O; Hutchinson, Alistair P; Nicklin, Stephen

    2015-08-01

    Polyclonal and monoclonal antibodies were raised to protein carrier molecules haptenized with RDX, a major component of many plastic explosives including Semtex. Sera from immunized mice detected RDX protein conjugates in standard ELISA. Clonally purified monoclonal antibodies had detection limits in the sub-ng/mL range for underivatized RDX in competition ELISA. The monoclonal antibodies are not dependent on the presence of taggants added during the manufacturing process, and are likely to have utility in the detection of any explosive containing RDX, or RDX contamination of environmental sites.

  13. Monoclonal antibodies and Fc fragments for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Eisenbeis AM

    2012-01-01

    Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

  14. A monoclonal antibody toolkit for C. elegans.

    Directory of Open Access Journals (Sweden)

    Gayla Hadwiger

    Full Text Available BACKGROUND: Antibodies are critical tools in many avenues of biological research. Though antibodies can be produced in the research laboratory setting, most research labs working with vertebrates avail themselves of the wide array of commercially available reagents. By contrast, few such reagents are available for work with model organisms. METHODOLOGY/PRINCIPAL FINDINGS: We report the production of monoclonal antibodies directed against a wide range of proteins that label specific subcellular and cellular components, and macromolecular complexes. Antibodies were made to synaptobrevin (SNB-1, a component of synaptic vesicles; to Rim (UNC-10, a protein localized to synaptic active zones; to transforming acidic coiled-coil protein (TAC-1, a component of centrosomes; to CENP-C (HCP-4, which in worms labels the entire length of their holocentric chromosomes; to ORC2 (ORC-2, a subunit of the DNA origin replication complex; to the nucleolar phosphoprotein NOPP140 (DAO-5; to the nuclear envelope protein lamin (LMN-1; to EHD1 (RME-1 a marker for recycling endosomes; to caveolin (CAV-1, a marker for caveolae; to the cytochrome P450 (CYP-33E1, a resident of the endoplasmic reticulum; to beta-1,3-glucuronyltransferase (SQV-8 that labels the Golgi; to a chaperonin (HSP-60 targeted to mitochondria; to LAMP (LMP-1, a resident protein of lysosomes; to the alpha subunit of the 20S subcomplex (PAS-7 of the 26S proteasome; to dynamin (DYN-1 and to the alpha-subunit of the adaptor complex 2 (APA-2 as markers for sites of clathrin-mediated endocytosis; to the MAGUK, protein disks large (DLG-1 and cadherin (HMR-1, both of which label adherens junctions; to a cytoskeletal linker of the ezrin-radixin-moesin family (ERM-1, which localized to apical membranes; to an ERBIN family protein (LET-413 which localizes to the basolateral membrane of epithelial cells and to an adhesion molecule (SAX-7 which localizes to the plasma membrane at cell-cell contacts. In addition to

  15. Generation and characterization of monoclonal antibodies specific to Coenzyme A

    Directory of Open Access Journals (Sweden)

    Malanchuk O. M.

    2015-06-01

    Full Text Available Aim. Generation of monoclonal antibodies specific to Coenzyme A. Methods. Hybridoma technique. KLH carrier protein conjugated with CoA was used for immunization. Screening of positive clones was performed with BSA conjugated to CoA. Results. Monoclonal antibody that specifically recognizes CoA and CoA derivatives, but not its precursors ATP and cysteine has been generated. Conclusion. In this study, we describe for the first time the production and characterization of monoclonal antibodies against CoA. The monoclonal antibody 1F10 was shown to recognize specifically CoA in Western blotting, ELISA and immunoprecipitation. These properties make this antiboby a particularly valuable reagent for elucidating CoA function in health and disease.

  16. Generation of monoclonal antibodies to native active human glycosyltransferases

    DEFF Research Database (Denmark)

    Vester-Christensen, Malene Bech; Bennett, Eric Paul; Clausen, Henrik;

    2013-01-01

    using monoclonal antibodies therefore provides an excellent strategy to analyze the glycosylation process in cells. A major drawback has been difficulties in generating antibodies to glycosyltransferases and validating their specificities. Here we describe a simple strategy for generating...

  17. Monoclonal antibody disulfide reduction during manufacturing

    Science.gov (United States)

    Hutterer, Katariina M.; Hong, Robert W.; Lull, Jonathon; Zhao, Xiaoyang; Wang, Tian; Pei, Rex; Le, M. Eleanor; Borisov, Oleg; Piper, Rob; Liu, Yaoqing Diana; Petty, Krista; Apostol, Izydor; Flynn, Gregory C.

    2013-01-01

    Manufacturing-induced disulfide reduction has recently been reported for monoclonal human immunoglobulin gamma (IgG) antibodies, a widely used modality in the biopharmaceutical industry. This effect has been tied to components of the intracellular thioredoxin reduction system that are released upon cell breakage. Here, we describe the effect of process parameters and intrinsic molecule properties on the extent of reduction. Material taken from cell cultures at the end of production displayed large variations in the extent of antibody reduction between different products, including no reduction, when subjected to the same reduction-promoting harvest conditions. Additionally, in a reconstituted model in which process variables could be isolated from product properties, we found that antibody reduction was dependent on the cell line (clone) and cell culture process. A bench-scale model using a thioredoxin/thioredoxin reductase regeneration system revealed that reduction susceptibility depended on not only antibody class but also light chain type; the model further demonstrates that the trend in reducibility was identical to DTT reduction sensitivity following the order IgG1λ > IgG1κ > IgG2λ > IgG2κ. Thus, both product attributes and process parameters contribute to the extent of antibody reduction during production. PMID:23751615

  18. Monoclonal antibodies based on hybridoma technology.

    Science.gov (United States)

    Yagami, Hisanori; Kato, Hiroshi; Tsumoto, Kanta; Tomita, Masahiro

    2013-03-01

    Based on the size and scope of the present global market for medicine, monoclonal antibodies (mAbs) have a very promising future, with applications for cancers through autoimmune ailments to infectious disease. Since mAbs recognize only their target antigens and not other unrelated proteins, pinpoint medical treatment is possible. Global demand is dramatically expanding. Hybridoma technology, which allows production of mAbs directed against antigens of interest is therefore privileged. However, there are some pivotal points for further development to generate therapeutic antibodies. One is selective generation of human mAbs. Employment of transgenic mice producing human antibodies would overcome this problem. Another focus is recognition sites and conformational epitopes in antigens may be just as important as linear epitopes, especially when membrane proteins such as receptors are targeted. Recognition of intact structures is of critical importance for medical purposes. In this review, we describe patent related information for therapeutic mAbs based on hybridoma technology and also discuss new advances in hybridoma technology that facilitate selective production of stereospecific mAbs.

  19. A monoclonal antibody against human MUDENG protein.

    Science.gov (United States)

    Wagley, Yadav; Choi, Jun-Ha; Wickramanayake, Dimuthu Dhammika; Choi, Geun-Yeol; Kim, Chang-Kyu; Kim, Tae-Hyoung; Oh, Jae-Wook

    2013-08-01

    MUDENG (mu-2-related death-inducing gene, MuD) encodes a predicted ∼54-kDa protein in humans, considered to be involved in trafficking proteins from endosomes toward other membranous compartments as well as in inducing cell death. Here we report on the generation of a mouse monoclonal antibody (MAb) against the middle domain of human (h) MuD. This IgG sub 1 MAb, named M3H9, recognizes residues 244-326 in the middle domain of the MuD protein. Thus, the MuD proteins expressed in an astroglioma cell line and primary astrocytes can be detected by the M3H9 MAb. We showed that M3H9 MAb can be useful in enzyme-linked immunosorbent assay (ELISA) and immunoblot experiments. In addition, M3H9 MAb can detect the expression of the MuD protein in formalin-fixed, paraffin-embedded mouse ovary and uterus tissues. These results indicate that the MuD MAb M3H9 could be useful as a new biomarker of hereditary spastic paraplegia and other related diseases.

  20. Drug Development of Therapeutic Monoclonal Antibodies.

    Science.gov (United States)

    Mould, Diane R; Meibohm, Bernd

    2016-08-01

    Monoclonal antibodies (MAbs) have become a substantial part of many pharmaceutical company portfolios. However, the development process of MAbs for clinical use is quite different than for small-molecule drugs. MAb development programs require careful interdisciplinary evaluations to ensure the pharmacology of both the MAb and the target antigen are well-understood. Selection of appropriate preclinical species must be carefully considered and the potential development of anti-drug antibodies (ADA) during these early studies can limit the value and complicate the performance and possible duration of preclinical studies. In human studies, many of the typical pharmacology studies such as renal or hepatic impairment evaluations may not be needed but the pharmacokinetics and pharmacodynamics of these agents is complex, often necessitating more comprehensive evaluation of clinical data and more complex bioanalytical assays than might be used for small molecules. This paper outlines concerns and strategies for development of MAbs from the early in vitro assessments needed through preclinical and clinical development. This review focuses on how to develop, submit, and comply with regulatory requirements for MAb therapeutics.

  1. Monoclonal Antibodies Against Xenopus Greatwall Kinase

    Science.gov (United States)

    Wang, Ling; Fisher, Laura A.; Wahl, James K.

    2011-01-01

    Mitosis is known to be regulated by protein kinases, including MPF, Plk1, Aurora kinases, and so on, which become active in M-phase and phosphorylate a wide range of substrates to control multiple aspects of mitotic entry, progression, and exit. Mechanistic investigations of these kinases not only provide key insights into cell cycle regulation, but also hold great promise for cancer therapy. Recent studies, largely in Xenopus, characterized a new mitotic kinase named Greatwall (Gwl) that plays essential roles in both mitotic entry and maintenance. In this study, we generated a panel of mouse monoclonal antibodies (MAbs) specific for Xenopus Gwl and characterized these antibodies for their utility in immunoblotting, immunoprecipitation, and immunodepletion in Xenopus egg extracts. Importantly, we generated an MAb that is capable of neutralizing endogenous Gwl. The addition of this antibody into M-phase extracts results in loss of mitotic phosphorylation of Gwl, Plk1, and Cdk1 substrates. These results illustrate a new tool to study loss-of-function of Gwl, and support its essential role in mitosis. Finally, we demonstrated the usefulness of the MAb against human Gwl/MASTL. PMID:22008075

  2. Development of syngeneic monoclonal anti-idiotype antibodies to mouse monoclonal anti-asialoglycoprotein receptor antibody.

    Directory of Open Access Journals (Sweden)

    Hirai M

    2002-06-01

    Full Text Available Anti-idiotype antibodies (Ab2 play an important role in the homeostasis of immune responses and are related to the development and the disease activity of certain autoimmune diseases. The asialoglycoprotein receptor (ASGPR is considered one of the target antigens in the pathogenesis of autoimmune chronic active hepatitis (AIH. We previously developed a mouse monoclonal antibody (clone 8D7 which recognizes rat and human ASGPR. In this study, to help investigate the anti-ASGPR antibody-anti-idiotype antibody network in patients with AIH, we developed a syngeneic mouse monoclonal Ab2 to the 8D7 anti-ASGPR antibody (Ab1. One clone, designated as 3C8, tested positive for specific reactivity to 8D7-Ab1 and did not bind to other irrelevant immunoglobulins. By competitive inhibition assays, the binding of 8D7-Ab1 to liver membrane extracts, i.e., the crude antigen preparation, was inhibited by 3C8-Ab2 in a dose-dependent manner, and the binding of 8D7-Ab1 to 3C8-Ab2 was inhibited by the liver membrane extracts. In the immunohistochemical analysis, 3C8-Ab2 blocked the specific staining of sinusoidal margins of rat hepatocytes by 8D7-Ab1. These results suggest that 3C8 anti-idiotype antibody recognizes the specific idiotypic determinants within the antigen-binding site of 8D7-Ab1.

  3. Early ROS-mediated DNA damage and oxidative stress biomarkers in Monoclonal B Lymphocytosis.

    Science.gov (United States)

    Collado, Rosa; Oliver, Isabel; Tormos, Carmen; Egea, Mercedes; Miguel, Amparo; Cerdá, Concha; Ivars, David; Borrego, Silvia; Carbonell, Felix; Sáez, Guillermo T

    2012-04-28

    Monoclonal B Lymphocytosis (MBL) is defined as asymptomatic monoclonal B-cell expansion characterised by a CLL-phenotype, but with less than 5×10(9)/l circulating cells. Reactive oxygen species (ROS)-mediated cell damage plays a critical role in the initiation of carcinogenesis as well as in malignant transformation. The goal of this study was to perform an analysis of the oxidative stress statuses of patients affected by MBL and chronic lymphocytic leukaemia (CLL). We examined peripheral blood and urine specimens from 29 patients with MBL, 55 with CLL and 31 healthy subjects. There was a significant increase in the occurrence of the mutagenic base 8-oxo-2'-deoxiguanosine (8-oxo-dG) in the lymphocytes and urine of MBL and CLL patients compared with controls. Significant differences were also observed in the levels of the lipid peroxidation product malondialdehyde (MDA) and in the oxidised/reduced glutathione (GSSG/GSH) ratio, although an increase in 8-isoprostane was not detected. Interestingly, the antioxidant catalase activity of circulating lymphocytes decreased in the patient groups. In conclusion, early oxidative stress exists in patients with MBL and CLL, causing damage to DNA and lipid structures. The higher levels of 8-oxo-dG in lymphocytes than in urine may be related to a decrease in the capacity of DNA repair systems. There were no differences in the oxidative statuses of the MBL and CLL patients, suggesting that oxidative injuries appear during a pre-leukaemic state of the disease.

  4. B-Cell Hematologic Malignancy Vaccination Registry

    Science.gov (United States)

    2016-12-28

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  5. Monoclonal antibodies against naturally occurring bioactive compounds.

    Science.gov (United States)

    Shoyama, Y; Tanaka, H; Fukuda, N

    1999-09-01

    The ratio of hapten to bovine serum albumin (BSA) in an antigen conjugate was determined by matrix-assisted laser desorption/ionization (MALDI) tof mass spectrometry. A hybridoma secreting monoclonal antibody (MAb) was produced by fusing splenocytes immunized with an antigen-BSA conjugate with HAT-sensitive mouse myeloma cells. The cross-reaction of anti-forskolin antibodies with 7-deacetyl forskolin was 5.6%. A very small cross-reaction appeared with other derivatives. The full measuring range of the assay extends from 5 ng to 5 mug/ml of forskolin. Immunoaffinity column chromatography using anti-forskolin MAbs appears to be far superior to previously published separation methods. The capacity of the immunoaffinity column as determined by ELISA is 9 mug/ml. Forskolin has been isolated directly from the crude extracts of tuberous roots and the callus culture of Coleus forskohlii. A MAb against tetrahydrocannabinolic acid (THCA) was produced. The cross-reaction of anti-THCA antibody against other cannabinoids was very wide. Many cannabinoids and a spiro-compound were reactive, but did not react with other phenolics. It became evident that this ELISA was able to be applied to the biotransformation experiments of cannabinoids in plant tissue culture system. Anti-ginsenoside Rb1 MAbs were produced. New western blotting method of determination for ginsenosides was established. Ginsenosides separated by silica gel TLC were transferred to a polyvinylidene difluoride (PVDF) membrane. The membrane was treated with NaIO(4) solution followed by BSA, resulting in a ginsenoside-BSA conjugate. Immunostaining of ginsenosides was more sensitive compared to other staining. Immunostaining of ginsenosides in the fresh ginseng root was succeeded using anti-ginsenoside Rb1 (GRb1) MAb after blotting to PVDF membrane.

  6. Production and characterization of monoclonal antibodies specific for canine CD138 (syndecan-1) for nuclear medicine preclinical trials on spontaneous tumours

    OpenAIRE

    Diab, Maya; Nguyen, Frédérique; Berthaud, Maxime; Maurel, Catherine; Gaschet, J.; Verger, Elise; Ibisch, Catherine; Chérel, Michel; Abadie, Jérôme; Davodeau, François; Rousseau, Caroline

    2016-01-01

    International audience; We isolated 11 antibodies specific for canine CD138 (cCD138) to validate the interest of CD138 antigen targeting in dogs with spontaneous mammary carcinoma. The affinity of the monoclonal antibodies in the nanomolar range is suitable for immunohistochemistry and nuclear medicine applications. Four distinct epitopes were recognized on cCD138 by this panel of antibodies. CD138 expression in canine healthy tissues is comparable to that reported in humans. CD138 is frequen...

  7. [Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People].

    Science.gov (United States)

    Simopoulos, Artemis P; Bourne, Peter G; Faergeman, Ole

    2013-11-01

    The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October-2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD's) worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

  8. Bellagio report on healthy agriculture, healthy nutrition, healthy people.

    Science.gov (United States)

    Simopoulos, Artemis P; Bourne, Peter G; Faergeman, Ole

    2013-02-05

    The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October-2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD's) worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

  9. Bellagio report on Healthy agriculture, healthy nutrition, healthy people⋆

    Directory of Open Access Journals (Sweden)

    Simopoulos Artemis P.

    2013-07-01

    Full Text Available The Bellagio Report on Healthy agriculture, healthy nutrition, healthy people is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October–2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD’s worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

  10. Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People

    Directory of Open Access Journals (Sweden)

    Ole Faergeman

    2013-02-01

    Full Text Available The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October–2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD’s worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

  11. Expect Respect: Healthy Relationships

    Science.gov (United States)

    ... Pediatrician Ages & Stages Prenatal Baby Toddler Preschool Gradeschool Teen Dating & Sex Fitness Nutrition Driving Safety School Substance Abuse Young Adult Healthy Children > Ages & Stages > Teen > Dating & Sex > Expect Respect: Healthy Relationships Ages & Stages Listen Español ...

  12. Healthy Environments for Children

    Science.gov (United States)

    ... OUTSIDE, THEY NEED CARE AND AFFECTION IN A HEALTHY ENVIRONMENT! ...AT SCHOOL... 2 ...AT HOME... ...EVEN IN THEIR ... CAN WE DO? HOW CAN WE GUARANTEE A HEALTHY FUTURE FOR ... PROTECTING THE ENVIRONMENT, ESPECIALLY RIVERS AND FORESTS, WE CAN IMPROVE THE ...

  13. A human monoclonal antibody to high-frequency red cell antigen Jra.

    Science.gov (United States)

    Miyazaki, T; Kwon, K W; Yamamoto, K; Tone, Y; Ihara, H; Kato, T; Ikeda, H; Sekiguchi, S

    1994-01-01

    A human-mouse heterohybridoma (HMR0921) secreting human monoclonal IgG3, lambda antibody was produced from peripheral blood lymphocytes of a healthy blood donor with serum antibody to Jra, by EBV transformation and hybridization with mouse myeloma cell line P3X63Ag8.653. The reactivity of HMR0921 antibody was assessed by antiglobulin test with a panel of red cells including 14 different rare blood types. Only Jr(a-) red cells were negative. The strict specificity of this antibody to Jra antigen was further confirmed by absorption test with fluorescence flow cytometry. On screening of 28,744 blood donor samples by HMR0921 antibody, we detected 19 agglutination-negative samples, which were confirmed as Jr(a-) by conventional anti-Jra antisera. Therefore, our HMR0921 antibody is extremely useful for detecting rare Jr(a-) blood.

  14. Thalassemia: Healthy Living

    Science.gov (United States)

    ... Thalassemia” More What can a person living with thalassemia do to stay healthy? A healthy lifestyle is ... disorder”, as well as making healthy choices. Managing Thalassemia Thalassemia is a treatable disorder that can be ...

  15. Healthy,Happy trees

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Healthy trees are important to us all. Trees provide shade, beauty, and homes for wildlife. Trees give us products like paper and wood. Trees can give us all this only if they are healthy.They must be well cared for to remain healthy.

  16. Preparation and Identification of Anti-rabies Virus Monoclonal Antibodies

    Institute of Scientific and Technical Information of China (English)

    Wen-juan Wang; Xiong Li; Li-hua Wang; Hu Shan; Lei Cao; Peng-cheng Yu; Qing Tang; Guo-dong Liang

    2012-01-01

    To provide a foundation for the development of rapid and specific methods for the diagnosis of rabies virus infection,anti-rabies virus monoclonal antibodies were prepared and rabies virus nucleoprotein and human rabies virus vaccine strain (PV strain) were used as immunogens to immunize 6-8 week old female BALB/c mice.Spleen cells and SP2/0 myeloma cells were fused according to conventional methods:the monoclonal cell strains obtained were selected using the indirect immunofluorescence test; this was followed by preparation of monoclonal antibody ascitic fluid; and finally,systematic identification of subclass,specificity and sensitivity was carried out.Two high potency and specific monoclonal antibodies against rabies virus were obtained and named 3B12 and 4A12,with ascitic fluid titers of 1∶8000 and 1∶10000,respectively.Both belonged to the IgG2a subclass.These strains secrete potent,stable and specific anti-rabies virus monoclonal antibodies,which makes them well suited for the development of rabies diagnosis reagents.

  17. A Strategy for Screening Monoclonal Antibodies for Arabidopsis Flowers

    Science.gov (United States)

    Shi, Qian; Zhou, Lian; Wang, Yingxiang; Ma, Hong

    2017-01-01

    The flower is one of the most complex structures of angiosperms and is essential for sexual reproduction. Current studies using molecular genetic tools have made great advances in understanding flower development. Due to the lack of available antibodies, studies investigating the localization of proteins required for flower development have been restricted to use commercial antibodies against known antigens such as GFP, YFP, and FLAG. Thus, knowledge about cellular structures in the floral organs is limited due to the scarcity of antibodies that can label cellular components. To generate monoclonal antibodies that can facilitate molecular studies of the flower, we constructed a library of monoclonal antibodies against antigenic proteins from Arabidopsis inflorescences and identified 61 monoclonal antibodies. Twenty-four of these monoclonal antibodies displayed a unique band in a western blot assay in at least one of the examined tissues. Distinct cellular distribution patterns of epitopes were detected by these 24 antibodies by immunofluorescence microscopy in a flower section. Subsequently, a combination of immunoprecipitation and mass spectrometry analysis identified potential targets for three of these antibodies. These results provide evidence for the generation of an antibody library using the total plant proteins as antigens. Using this method, the present study identified 61 monoclonal antibodies and 24 of them were efficiently detecting epitopes in both western blot experiments and immunofluorescence microscopy. These antibodies can be applied as informative cellular markers to study the biological mechanisms underlying floral development in plants. PMID:28293248

  18. Healthy cities and healthy urban design

    OpenAIRE

    Drevland, Ingvill S.

    2016-01-01

    As an occupational therapist, I have always found the interaction between humans, their environment and their activities interesting, and how the environment can influence what we do and our occupational patterns is something that fascinates me. As my interest for urban health and healthy cities has grown during this master program, I have chosen to use the experience and knowledge I have from my field of expertise and put it in the context of healthy urban planning. This maste...

  19. Action plan for healthy agriculture, healthy nutrition, healthy people

    Directory of Open Access Journals (Sweden)

    Artemis P. Simopoulos

    2013-04-01

    Full Text Available In October 2010, the World Council on Genetics, Nutrition and Fitness for Health promoted a scientific meeting in Ancient Olympia, Greece, on the theme Healthy Agriculture, Healthy Nutrition, Healthy People. The meeting focused on evolutionary aspects of human diet through the life cycle in terms of genetic predisposition, overall health, prevention of disease and of unhealthy behaviors, such as poor physical activity, and dietary changes caused by the introduction of modern agriculture, from the Agribusiness to systems of food production, from climate changes to the needs imposed by urban agriculture and architecture. Nutritional medical (mostly cardiological and political aspects of disease prevention through healthy dietary habits and physical activity have always been seen in isolation. The meeting, the first of its kind, treated such aspects together, recognizing the importance of integrating and initiating a dialogue between these disciplines. The meeting gathered together experts in cardiovascular prevention, nutrition, as well as politicians, for a global discussion of these themes. A summary statement was then compiled, focusing on the main themes on which a consensus had been reached. I strongly believe that such themes have great relevance for public health, raising the need for disseminating them as widely as possible. I am thankful to the Editor of the Italian Journal of Medicine for allowing this summary document to be made available for the first time in Italy.Raffaele De Caterina

  20. Immunoblotting with monoclonal antibodies: importance of the blocking solution.

    Science.gov (United States)

    Hauri, H P; Bucher, K

    1986-12-01

    Four commonly used blocking agents, i.e., fetal calf serum, mammalian gelatin-Nonidet-P40, fish gelatin-Nonidet-P40, and defatted powdered milk were compared with respect to their efficiency to block the nonspecific background and to promote maximal immunoreactivity of monoclonal antibodies against human intestinal sucrase-isomaltase during immunoblotting. Two of five monoclonal antibodies were found to react with the electroblotted enzyme. However, one of the reacting antibodies gave optimal results with fish gelatin-Nonidet-P40 and the other with defatted powdered milk, while fetal calf serum lead to unacceptably high backgrounds. The results suggest that some of the difficulties encountered with monoclonal antibodies in immunoblotting may be due to inappropriate blocking conditions.

  1. ELISA Detection of Francisella tularensis using Polyclonaland Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2008-09-01

    Full Text Available The mouse monoclonal and polyclonal antibodies were produced for the detection of intracellular pathogenand potential warfare agent Francisella tularensis. Antibody titers obtained were 1:640 for polyclonal antibodiesand 1:320 for monoclonal antibodies. Both antibodies were used in the indirect enzyme-linked immunosorbentassay (ELISA found to detect F. tularensis whole cells. The limit of detection was 5.4×106 CFU/ml for polyclonalantibodies and 6.9×106 CFU/ml for monoclonal antibodies. The value sample could  be distinguished from anyconcentration of another gram-negative bacterium: Escherichia coli.Defence Science Journal, 2008, 58(5, pp.698-702, DOI:http://dx.doi.org/10.14429/dsj.58.1693

  2. The Case for Adjunctive Monoclonal Antibody Immunotherapy in Schizophrenia.

    Science.gov (United States)

    Miller, Brian J; Buckley, Peter F

    2016-06-01

    This article presents the case in favor of clinical trials of adjunctive monoclonal antibody immunotherapy in schizophrenia. Evidence for prenatal and premorbid immune risk factors for the development of schizophrenia in the offspring is highlighted. Then key evidence for immune dysfunction in patients with schizophrenia is considered. Next, previous trials of adjunctive anti-inflammatory or other immunotherapy in schizophrenia are discussed. Then evidence for psychosis as a side effect of immunotherapy for other disorders is discussed. Also presented is preliminary evidence for adjunctive monoclonal antibody immunotherapy in psychiatric disorders. Finally, important considerations in the design and implementation of clinical trials of adjunctive monoclonal antibody immunotherapy in schizophrenia are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Science.gov (United States)

    Fiala, Mark; Slade, Michael; Westervelt, Peter

    2017-01-01

    Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM. PMID:28316846

  4. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Directory of Open Access Journals (Sweden)

    Bita Fakhri

    2017-01-01

    Full Text Available Posttransplant Lymphoproliferative Disorder (PTLD is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT. Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML. Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM; thus a diagnosis of smoldering multiple myeloma (SMM was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

  5. Therapeutic monoclonal antibodies in human breast milk: a case study.

    Science.gov (United States)

    Ross, Elle; Robinson, Steven E; Amato, Carol; McMillan, Colette; Westcott, Jay; Wolf, Tiffany; Robinson, William A

    2014-04-01

    Recently, therapeutic monoclonal antibodies have been introduced for the treatment of advanced melanoma and other diseases. It remains unclear whether these drugs can be safely administered to women who are breast feeding because of the potential hazardous side effects for nursing infants. One such therapy for metastatic melanoma is ipilimumab, a human monoclonal antibody that blocks cytotoxic T-lymphocyte-antigen-4, and is the preferred treatment for patients with metastatic melanoma when other molecular therapies are not viable. This study measured ipilimumab levels in the breast milk of a patient undergoing treatment that were enough to raise concerns for a nursing infant exposed to ipilimumab.

  6. ERBB oncogene proteins as targets for monoclonal antibodies.

    Science.gov (United States)

    Polanovski, O L; Lebedenko, E N; Deyev, S M

    2012-03-01

    General properties of the family of tyrosine kinase ERBB receptors are considered in connection with their role in the generation of cascades of signal transduction in normal and tumor cells. Causes of acquisition of oncogene features by genes encoding these receptors and their role in tumorigenesis are analyzed. Anti-ERBB monoclonal antibodies approved for therapy are described in detail, and mechanisms of their antitumor activity and development of resistance to them are reviewed. The existing and the most promising strategies for creating and using monoclonal antibodies and their derivatives for therapy of cancer are discussed.

  7. Quantitative analysis of monoclonal antibodies by cation-exchange chromatofocusing.

    Science.gov (United States)

    Rozhkova, Anna

    2009-08-07

    A robust cation-exchange chromatofocusing method was developed for the routine analysis of a recombinant humanized monoclonal IgG antibody. We compare the chromatofocusing method to the conventional cation-exchange chromatography (CEX) employing a salt gradient and show clear advantages of chromatofocusing over CEX. We demonstrate the suitability of the present chromatofocusing method for its intended purpose by testing the validation characteristics. To our knowledge, this is the first chromatofocusing method developed for the routine analysis of monoclonal antibody charge species.

  8. Purification of Murine Monoclonal IgM Antibody

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    This paper presents the purification of a monoclonal IgM antibody against human tumor associated antigen Lewis-Y by ion exchange chromatography and gel filtration.Enzyme-linked immunosorbent assay (ELISA) and SDS-polyacrylamide gel electrophoresis (PAGE) were used to identify purified IgM antibody.In flow cytometry analysis, the purified IgM antibody recognizes human breast tumor cell line MCF-7 which expresses Lewis-Y antigen.This work presents a new way for the purification of murine monoclonal IgM antibody.

  9. High throughput production of mouse monoclonal antibodies using antigen microarrays

    DEFF Research Database (Denmark)

    De Masi, Federico; Chiarella, P.; Wilhelm, H.;

    2005-01-01

    Recent advances in proteomics research underscore the increasing need for high-affinity monoclonal antibodies, which are still generated with lengthy, low-throughput antibody production techniques. Here we present a semi-automated, high-throughput method of hybridoma generation and identification....... Monoclonal antibodies were raised to different targets in single batch runs of 6-10 wk using multiplexed immunisations, automated fusion and cell-culture, and a novel antigen-coated microarray-screening assay. In a large-scale experiment, where eight mice were immunized with ten antigens each, we generated...

  10. Radiolabelled peptides and monoclonal antibodies for therapy decision making in inflammatory diseases

    NARCIS (Netherlands)

    Malviya, G.; Signore, A.; Lagana, B.; Dierckx, R. A.

    2008-01-01

    Radiolabelled peptides and monoclonal antibodies are an emerging class of radiopharmaceuticals for imaging inflammation with clinical implications for several chronic inflammatory disorders for diagnosis, therapy decision making and follow up. In the last decades, a number of novel monoclonal antibo

  11. Are there healthy obese?

    Science.gov (United States)

    Griera Borrás, José Luis; Contreras Gilbert, José

    2014-01-01

    It is currently postulated that not all obese individuals have to be considered as pathological subjects. From 10% to 20% of obese people studied do not show the metabolic changes common in obese patients. The term "healthy obese" has been coined to refer to these patients and differentiate them from the larger and more common group of pathological obese subjects. However, the definition of "healthy obese" is not clear. Use of "healthy obese" as a synonym for obese without metabolic complications is risky. Clinical markers such as insulin resistance are used to identify this pathology. It is not clear that healthy obese subjects have lower morbidity and mortality than pathologically obese patients. According to some authors, healthy obese would represent an early stage in evolution towards pathological obesity. There is no agreement as to the need to treat healthy obese subjects. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  12. ADOLESCENTS’ HEALTHY EATING

    DEFF Research Database (Denmark)

    Pedersen, Susanne

    . As a follow-up on a healthy eating intervention, 38 adolescents and their respective families participated in depth-interviews and a practical exercise on daily fruit and vegetable intake. Results demonstrated that adolescents were found to adopt two strategies: a direct one placing demands on parents......This PhD thesis contributes with knowledge about adolescent healthy eating by studying consumer socialisation, social influence and behavioural change in relation to adolescent healthy eating. The introduction provides the important reasons for studying adolescents and healthy eating and explains...... that a more holistic approach is needed in order to respond to the rising levels of overweight among adolescents. It is important to understand the development of and influences on adolescent healthy eating behaviour and the possibilities for promoting healthy eating through interventions. By reviewing...

  13. Monoclonal antibodies in animal production; their use in diagnostics and passive immunization.

    NARCIS (Netherlands)

    Booman, P.

    1989-01-01

    One of the landmarks in immunology was the invention and development of monoclonal antibody-secreting hybridomas by Milstein and his coworkers. The enormous promise of monoclonal antibody technology, which became apparent soon after its discovery, may explain the unusual speed with which monoclonal

  14. Characterization of Binding Epitopes of CA125 Monoclonal Antibodies

    DEFF Research Database (Denmark)

    Marcos-Silva, Lara; Narimatsu, Yoshiki; Halim, Adnan

    2014-01-01

    The most used cancer serum biomarker is the CA125 immunoassay for ovarian cancer that detects the mucin glycoprotein MUC16. Several monoclonal antibodies (mAbs) including OC125 and M11 are used in CA125 assays. However, despite considerable efforts, our knowledge of the molecular characteristics...

  15. Production and characterization of monoclonal antibodies against mink leukocytes

    DEFF Research Database (Denmark)

    Chen, W.S.; Pedersen, Mikael; Gram-Nielsen, S.

    1997-01-01

    Three monoclonal antibodies (mAbs) were generated against mink leukocytes. One antibody reacted with all T lymphocytes, one with all monocytes and one had platelet reactivity. Under reducing conditions, the T lymphocyte reactive antibody immunoprecipitated 18 kDa, 23 kDa, 25 kDa and 32-40 kDa pol...

  16. Production and potential use of monoclonal antibodies against polio viruses.

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); A.L. van Wezel; G. van Steenis (Bert); A.G. Hazendonk

    1982-01-01

    textabstractLymphocyte hybridomas secreting monoclonal antibodies against different strains of polio virus type 1, 2, or 3 have been produced. For this purpose Balb/C mice were immunized with purified and inactivated virus suspensions and their splenocytes were fused with P3X63Ag8 mouse myeloma cell

  17. Immunohistochemical diagnosis of systemic bovine zygomycosis by murine monoclonal antibodies

    DEFF Research Database (Denmark)

    Jensen, H.E.; Aalbaek, B.; Lind, Peter

    1996-01-01

    Murine monoclonal antibodies (Mabs) against water-soluble somatic antigens (WSSA) and the wall fraction (WF) from Rhizopus arrhizus (Rhizopus oryzae) were produced in vitro by fusion of splenocytes from immunized BALB/c mice with mouse myeloma X63-Ag 8.653 cells. Supernatants reacting only with h...... for the in situ diagnosis of systemic bovine zygomycosis....

  18. Medullary carcinomas of the thyroid: a monoclonal origin.

    Science.gov (United States)

    Marques, A R; Catarino, A L; Moniz, S; Cavaco, B; Roque, L; Sobrinho, L; Leite, V

    2001-12-01

    We studied the clonality of medullary thyroid carcinomas (MTC) from 16 female patients by determining X chromosome inactivation by polymerase chain reaction (PCR) amplification of a CAG repeat in exon 1 of the human androgen-receptor gene. One patient with sporadic medullary thyroid carcinoma (MTC) was homozygous for this microsatellite and was not considered for the assessment of clonality. Sixteen tumor samples from the informative 15 patients were studied: 11 were from sporadic cases and 5 were from familial cases (3 cases of multiple endocrine neoplasia type 2A [MEN 2A]; 1 case of familial medullary thyroid carcinoma [FMTC]). Fourteen tumor samples (10/11 sporadic, 3/4 MEN 2A and 1/1 FMTC) were clearly monoclonal with allelic cleavage ratios between 2.5 and 49.1. Sixty-four percent of these cases (9/14) had the preferential amplification of the shorter allele while 36 percent (5/14) had the preferential amplification of the longer allele. Two frozen tumor samples (1 sporadic and 1 MEN 2A) were polyclonal. However, the corresponding tumor embedded in paraffin from the sporadic case was monoclonal. The other polyclonal tumor was found in the right thyroid lobe of a patient with MEN 2A who had a monoclonal tumor in the left lobe. Our results clearly demonstrate that MTC have a monoclonal origin in the majority of the cases.

  19. A mouse monoclonal antibody against Alexa Fluor 647.

    Science.gov (United States)

    Wuethrich, Irene; Guillen, Eduardo; Ploegh, Hidde L

    2014-04-01

    Fluorophores are essential tools in molecular and cell biology. However, their application is mostly confined to the singular exploitation of their fluorescent properties. To enhance the versatility and expand the use of the fluorophore Alexa Fluor 647 (AF647), we generated a mouse monoclonal antibody against it. We demonstrate its use of AF647 for immunoblot, immunoprecipitation, and cytofluorimetry.

  20. Development of monoclonal antibodies that recognize Treponema pallidum.

    OpenAIRE

    Saunders, J M; Folds, J D

    1983-01-01

    We developed a panel of monoclonal antibodies to Treponema pallidum (Nichols) antigens, some of which recognize treponemal antigens on T. pallidum (Nichols), T. pallidum strain 14, and Treponema phagedenis biotype Reiter. The antibodies were detected by either an enzyme-linked immunosorbent assay or a radioimmunoassay.

  1. Monoclonal antibodies for the control of influenza virus vaccines.

    NARCIS (Netherlands)

    H.J.M. van de Donk; M.F. van Olderen; A.D.M.E. Osterhaus (Albert); J.C. de Jong (Jan)

    1984-01-01

    textabstractHybridomas producing haemagglutination inhibiting monoclonal antibodies against influenza A/Texas/1/77 H3N2 were developed. One hybridoma producing antibodies reacting with Victoria/3/75, Texas/1/77 Bangkok/1/79 and England/496/80 was selected to determine the potency of influenza virusv

  2. Monoclonal antibodies for the detection of Puccinia striiformis urediniospores

    DEFF Research Database (Denmark)

    Skottrup, Peter Durand; Frøkiær, Hanne; Hearty, Stephen

    2007-01-01

    The fungal pathogen Pst causes yellow rust disease in wheat plants leading to crop losses. The organism spreads by releasing wind-dispersed urediniospores from infected plants. In this study a library of novel monoclonal antibodies (mAbs) was developed against Pst urediniospores. Nine mAb-produci...

  3. Monoclonal Antibodies to Prevent Use of Mycotoxins as Biological Weapons

    Science.gov (United States)

    2007-07-01

    Mycotoxins as Biological Weapons PRINCIPAL INVESTIGATOR: Marta Feldmesser, M.D. CONTRACTING ORGANIZATION: Albert Einstein College of...Monoclonal Antibodies to Prevent Use of Mycotoxins as Biological Weapons 5b. GRANT NUMBER W81XWH-06-1-0085 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

  4. Monoclonal antibodies specific for the organophosphate pesticide azinphos-methyl

    NARCIS (Netherlands)

    Jones, WT; Harvey, D; Jones, SD; Ryan, GB; Wynberg, H; TenHoeve, W; Reynolds, PHS

    1995-01-01

    2-(2-Mercapto-5-methyl-1,3,2-dioxaphosphorinan-5-yl,2-sulphide) methoxyacetic acid has been synthesized and used to prepare an azinphos hapten and protein conjugates. Monoclonal antibodies of high affinity against the pesticide azinphos-methyl were prepared from mice immunized with the

  5. Generation and Characterization of Novel Human IRAS Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2009-01-01

    Full Text Available Imidazoline receptors were first proposed by Bousquet et al., when they studied antihypertensive effect of clonidine. A strong candidate for I1R, known as imidazoline receptor antisera-selected protein (IRAS, has been cloned from human hippocampus. We reported that IRAS mediated agmatine-induced inhibition of opioid dependence in morphine-dependent cells. To elucidate the functional and structure properties of I1R, we developed the newly monoclonal antibody against the N-terminal hIRAS region including the PX domain (10–120aa through immunization of BALB/c mice with the NusA-IRAS fusion protein containing an IRAS N-terminal (10–120aa. Stable hybridoma cell lines were established and monoclonal antibodies specifically recognized full-length IRAS proteins in their native state by immunoblotting and immunoprecipitation. Monoclonal antibodies stained in a predominantly punctate cytoplasmic pattern when applied to IRAS-transfected HEK293 cells by indirect immunofluorescence assays and demonstrated excellent reactivity in flow immunocytometry. These monoclonal antibodies will provide powerful reagents for the further investigation of hIRAS protein functions.

  6. MONOCLONAL ANTIBODIES TO IDENTIFY TOMATO MOSAIC TOBAMOVIRUS (TOMV

    Directory of Open Access Journals (Sweden)

    Duarte Keila M.R.

    2001-01-01

    Full Text Available Monoclonal antibodies were obtained against Tomato mosaic tobamovirus (ToMV isolated in Brazil. One antibody (8G7G2 isotyped as IgG2b (kappa light chain showed strong specificity and very low cross reaction with the Tobacco mosaic virus (TMV. It can be used in identification of tomato mosaic virus (ToMV.

  7. Serological comparison of tospovirus isolates using polyclonal and monoclonal antibodies.

    NARCIS (Netherlands)

    Adam, G.; Peters, D.; Goldbach, R.W.

    1996-01-01

    A test was conducted to compare tospovirus isolates using different poly- and monoclonal antibodies. All isolates and antibodies were compared under identical conditions. From 130 tospovirus isolates, which were obtained from all over the world and included well-characterized isolates from all four

  8. Serological comparison of tospovirus isolates using polyclonal and monoclonal antibodies.

    NARCIS (Netherlands)

    Adam, G.; Peters, D.; Goldbach, R.W.

    1996-01-01

    A test was conducted to compare tospovirus isolates using different poly- and monoclonal antibodies. All isolates and antibodies were compared under identical conditions. From 130 tospovirus isolates, which were obtained from all over the world and included well-characterized isolates from all four

  9. Monoclonal antibodies specific for the organophosphate pesticide azinphos-methyl

    NARCIS (Netherlands)

    Jones, WT; Harvey, D; Jones, SD; Ryan, GB; Wynberg, H; TenHoeve, W; Reynolds, PHS

    1995-01-01

    2-(2-Mercapto-5-methyl-1,3,2-dioxaphosphorinan-5-yl,2-sulphide) methoxyacetic acid has been synthesized and used to prepare an azinphos hapten and protein conjugates. Monoclonal antibodies of high affinity against the pesticide azinphos-methyl were prepared from mice immunized with the hapten-ovalbu

  10. Syngeneic anti-idiotypic monoclonal antibodies to an anti-NeuGc-containing ganglioside monoclonal antibody.

    Science.gov (United States)

    Vázquez, A M; Pérez, A; Hernández, A M; Macías, A; Alfonso, M; Bombino, G; Pérez, R

    1998-12-01

    An IgM monoclonal antibody (MAb), named P3, has the characteristic to react specifically with a broad battery of N-glycolyl containing-gangliosides and with antigens expressed on breast tumors. When this MAb was administered alone in syngeneic mice, an specific IgG anti-idiotypic antibody (Ab2) response was induced, this Ab2 response was increased when P3 MAb was injected coupled to a carrier protein and in the presence of Freund's adjuvant. Spleen cells from these mice were used in somatic-cell hybridization experiments, using the murine myeloma cell line P3-X63-Ag8.653 as fusion partner. Five Ab2 MAbs specific to P3 MAb were selected. These IgG1 Ab2 MAbs were able to block the binding of P3 MAb to GM3(NeuGc) ganglioside and to a human breast carcinoma cell line. Cross-blocking experiments demonstrated that these Ab2 MAbs are recognizing the same or very close sites on the Abl MAb. The five Ab2 MAbs were injected into syngeneic mice and four of them produced strong anti-anti-idiotypic antibody (Ab3) response. While these Ab2 MAbs were unable to generate Ab3 antibodies with the same antigenic specificity than P3 MAb, three of them induced antibodies bearing P3 MAb idiotopes (Ag-Id+ Ab3). These results demonstrated that these Ab2 MAbs are not "internal image" antibodies, but they could define "regulatory idiotopes."

  11. Healthy Homes Tools

    Science.gov (United States)

    Peek, Gina; Lyon, Melinda; Russ, Randall

    2012-01-01

    Extension is focusing on healthy homes programming. Extension educators are not qualified to diagnose consumers' medical problems as they relate to housing. We cannot give medical advice. Instead, we can help educate consumers about home conditions that may affect their well-being. Extension educators need appropriate healthy homes tools to…

  12. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  13. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  14. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of

  15. Active and Healthy Schools

    Science.gov (United States)

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  16. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of hu

  17. Heart-Healthy Exercise

    Science.gov (United States)

    ... American Heart Association Cardiology Patient Page Heart-Healthy Exercise Lauren Healey Mellett , Gisele Bousquet Download PDF https:// ... if you already have heart disease. How Can Exercise Help? There are many modifiable risk factors for ...

  18. Getting Healthy Scientifically

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Recently,Zhao Zhixin,a Beijing-based instructor on scientific bodybuilding and public sport,was interviewed by China Youth Daily,sharing his views on how to get healthy scientifically.Edited excerpts follow:

  19. Healthy Living after Stroke

    Science.gov (United States)

    ... Stories Stroke Heroes Among Us Healthy Living After Stroke Nutrition Good nutrition is one way to reduce ... look to maintain health and wellness. Subscribe to Stroke Connection Get quarterly digital issues plus our monthly ...

  20. Healthy Joints Matter

    Science.gov (United States)

    ... my joints more healthy? Definitions What can go wrong? Although you might think arthritis affects only older ... Discovery Into Health ® Home | Health Information | Research | Funding | News & Events | About Us | Portal en español | Asian-Language ...

  1. Healthy Eating and Pregnancy

    Science.gov (United States)

    ... Situations Pets and Animals myhealthfinder Food and Nutrition Healthy Food Choices Weight Loss and Diet Plans Nutrients and Nutritional Info Sugar and Sugar Substitutes Exercise and Fitness Exercise Basics Sports Safety Injury Rehabilitation Emotional Well- ...

  2. Healthy Watersheds Protection

    Science.gov (United States)

    Jump to main content US EPA United States Environmental Protection Agency Search Search Healthy Watersheds Protection (HWP) Share ... live in a watershed — thus watershed condition is important to everyone. Watersheds exist at different geographic scales, ...

  3. Healthy Ride Trip Data

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — A dataset that shows trips taken using the Healthy Ride system by quarter. The dataset includes bike number, membership type, trip start and end timestamp, and...

  4. Healthy Conflict Management

    OpenAIRE

    Brower, Naomi

    2012-01-01

    Without healthy conflict management skills, conflict can often escalate or intensify over time. This fact sheet gives tips on utilizing key negotiation skills to help individuals effectively address and cope with conflict and potentially build stronger relationships with others.

  5. Planning For a Healthy School Year: Healthy Eating

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Planning For A Healthy School Year Healthy Eating Past ... are one of the first items. Read More "Planning For A Healthy School Year" Articles Back to ...

  6. Coarse grained modeling of transport properties in monoclonal antibody solution

    Science.gov (United States)

    Swan, James; Wang, Gang

    Monoclonal antibodies and their derivatives represent the fastest growing segment of the bio pharmaceutical industry. For many applications such as novel cancer therapies, high concentration, sub-cutaneous injections of these protein solutions are desired. However, depending on the peptide sequence within the antibody, such high concentration formulations can be too viscous to inject via human derived force alone. Understanding how heterogenous charge distribution and hydrophobicity within the antibodies leads to high viscosities is crucial to their future application. In this talk, we explore a coarse grained computational model of therapeutically relevant monoclonal antibodies that accounts for electrostatic, dispersion and hydrodynamic interactions between suspended antibodies to predict assembly and transport properties in concentrated antibody solutions. We explain the high viscosities observed in many experimental studies of the same biologics.

  7. Healthy Lean Through HRD

    DEFF Research Database (Denmark)

    Jørgensen, Frances

    2008-01-01

    The paper reports on findings from the initial, exploratory phase of a longitudinal research study aimed at developing a framework for implementing lean while ensuring employee well-being. Data from observations and in-depth dialogues with persons involved in lean implementation, along...... with relevant theory, are used to construct a tentative framework for implementing "healthy lean". The role of HRD in facilitating implementation of healthy lean is central to the framework, which is presented and discussed....

  8. Production of monoclonal antibodies to human glomerular basement membrane.

    Directory of Open Access Journals (Sweden)

    Mino,Yasuaki

    1984-10-01

    Full Text Available Using the technique of somatic cell fusion, we produced monoclonal antibodies to collagenase-digested human glomerular basement membrane (GBM. Fourteen monoclonal antibodies which reacted with normal human kidney in indirect immunofluorescence (IIF studies were produced. An analysis of the binding patterns indicated that the antigens recognized could be divided into six broad groups. Monoclonal antibody B3-H10 (Group 1 reacted with only GBM in a fine granular pattern. A5-B12 and B5-C2 (Group 2 reacted with GBM and peritubular capillary in a linear pattern. B2-A12 (Group 3 reacted with only epithelial cells. Al-C9 and A4-E2 (Group 4 showed a mesangial pattern in glomerulus and a lineal pattern in tubular basement membrane (TBM, Bowman's capsule and peritubular capillary. A1-E1, A1-E11, A2-E6, A3-B6, A4-F8 and B5-H2 (Group 5 recognized determinants common to GBM, TBM, Bowman's capsule and/or peritubular capillary. A3-F1 and B5-E10 (Group 6 reacted with TBM and Bowman's capsule. The staining pattern of B3-H10 (Group 1 was characteristic because it was not linear, but finely granular along the GBM. The staining pattern of B2-A12 (Group 3 was also characteristic because only epithelial cells were stained, and processes of epithelial cells were observed as fine fibrils. To the best of our knowledge, these two types of monoclonal antibodies have not been reported previously.

  9. Strategies for Treating Autoimmune Disease With Monoclonal Antibodies

    OpenAIRE

    Wofsy, David

    1985-01-01

    There is no safe and reliable therapy for most serious autoimmune diseases, such as systemic lupus erythematosus. Severe cases usually require treatment with corticosteroids or cytotoxic drugs or both, which frequently provide inadequate disease control and can cause serious complications. These therapies are not restricted in their effects to cells of the immune system, but rather have a broad range of toxic effects on cells throughout the body. The development of monoclonal antibodies has l...

  10. Quantification of Moraxella bovis haemagglutinating adhesins with monoclonal antibodies.

    Science.gov (United States)

    Gil-Turnes, C; Aleixo, J A

    1991-08-01

    Six monoclonal antibodies (MAbs) against Moraxella bovis GF 9 were used to quantify haemagglutinating adhesins of 16 strains of this organism. The amount of each MAb necessary to inhibit one haemagglutinating unit of each strain varied between 4 and 0.007 times that required by strain GF 9. Five strains reacted with six MAbs, one with five, two with four, one with three, two with two and three with none. The procedures used enabled to detect dominant strains candidates for vaccines.

  11. Monoclonal antibody to native P39 protein from Borrelia burgdorferi.

    OpenAIRE

    Sullivan, T J; Hechemy, K E; Harris, H L; Rudofsky, U H; Samsonoff, W A; Peterson, A J; Evans, B. D.; Balaban, S L

    1994-01-01

    We have produced, by using a sonicate of Borrelia burgdorferi, a monoclonal antibody (MAb), NYSP39H, that is specific for the P39 protein band. This MAb reacted with 13 isolates of B. burgdorferi but not with eight different spirochetes (four borrelias, two leptospiras, and two treponemas). Surface labeling of B. burgdorferi with biotin and subsequent treatment with Nonidet P-40 showed that P39 was not biotinylated but was extracted with Nonidet P-40, indicating that it is present within the ...

  12. A monoclonal antibody for G protein-coupled receptor crystallography.

    Science.gov (United States)

    Day, Peter W; Rasmussen, Søren G F; Parnot, Charles; Fung, Juan José; Masood, Asna; Kobilka, Tong Sun; Yao, Xiao-Jie; Choi, Hee-Jung; Weis, William I; Rohrer, Daniel K; Kobilka, Brian K

    2007-11-01

    G protein-coupled receptors (GPCRs) constitute the largest family of signaling proteins in mammals, mediating responses to hormones, neurotransmitters, and senses of sight, smell and taste. Mechanistic insight into GPCR signal transduction is limited by a paucity of high-resolution structural information. We describe the generation of a monoclonal antibody that recognizes the third intracellular loop (IL3) of the native human beta(2) adrenergic (beta(2)AR) receptor; this antibody was critical for acquiring diffraction-quality crystals.

  13. Super-Genotype: Global Monoclonality Defies the Odds of Nature

    OpenAIRE

    Johannes J Le Roux; Wieczorek, Ania M.; Wright, Mark G.; Carol T Tran

    2007-01-01

    The ability to respond to natural selection under novel conditions is critical for the establishment and persistence of introduced alien species and their ability to become invasive. Here we correlated neutral and quantitative genetic diversity of the weed Pennisetum setaceum Forsk. Chiov. (Poaceae) with differing global (North American and African) patterns of invasiveness and compared this diversity to native range populations. Numerous molecular markers indicate complete monoclonality with...

  14. Recent Progress toward Engineering HIV-1-Specific Neutralizing Monoclonal Antibodies

    OpenAIRE

    Ming Sun; Yue Li; Huiwen Zheng; Yiming Shao

    2016-01-01

    The recent discoveries of broadly potent neutralizing human monoclonal antibodies represent a new generation of antiretrovirals for the treatment and prophylaxis. Antibodies are generally considered more effective and safer and have been proved to provide passive protection against mucosal challenge in humanized mice and macaques. Several neutralizing Abs could protect animals against HIV-1 but are not effective when used in an established infected model for therapy. In order to overcome the ...

  15. [Neutralizing Monoclonal and Chimeric Antibodies to Human IFN-γ].

    Science.gov (United States)

    Larina, M V; Aliev, T K; Solopova, O N; Pozdnyakova, L P; Korobova, S V; Yakimov, S A; Sveshnikov, P G; Dolgikh, D A; Kirpichnikov, M P

    2015-01-01

    Autoiminune disorders are chronic diseases characterized by abnormal immune response directed against self-antigens that leads to tissue damage and violation of its normal functioning. Such diseases often result in disability or even death of patients. Nowadays a number of monoclonal antibodies to pro-inflammatory cytokines and their receptors are successfully used for the targeted treatment of autoimmune diseases. One of the perspective targets in autoimmune disease therapy is interferon gamma, a key cytokine in Th1 cells differentiation, activation of macrophages, and inflammation. In the present work, 5 monoclonal antibodies to human IFN-γ were obtained. For the development of potential therapeutic agent, we have performed neutralizing activity and affinity analysis of the antibodies. Based on the data obtained, the monoclonal antibody F1 was selected. This antibody has a dissociation constant 1.7 x 10(-9) M and IC90 = 8.9 ± 2.0 nM measured upon antibody inhibition of the IFN-γ-induced HLA-DR expression on the surface of U937 cells. We have constructed a bicistronic vector for the production of recombinant chimeric Fab fragment F1 chim in E. coli cells. The recombinant chimeric Fab fragment Fl chim neutralizes IFN-γ activity in vitro and has a dissociation constant 1.8 x 10(-9) M.

  16. The Use of Monoclonal Antibodies in Human Prion Disease

    Science.gov (United States)

    Bodemer, Walter

    Detection of PrP and its pathological isoform(s) is the key to understanding the etiology and pathogenesis of transmissible spongiform encephalopathy. There is ample evidence that PrP isoforms constitute a major component of an unknown and perhaps unconventional infectious agent. An etiological relationship between human and zoonotic transmissible spongiform encephalopathies may be revealed with monoclonal antibodies. Knowledge of the conformational transition rendering a nonpathogenic, almost ubiquitous cellular protein into a pathogenic one is crucial to defining pathomechanisms. The stepwise or even continuous formation of pathogenic molecules can be monitored. Any improvement in the early diagnosis could help to conceive new therapeutic measures which are not currently available. Determination of PrP isoforms in tissue, cells, or body fluids may be of prognostic value. Many experimental approaches in molecular medicine and molecular biology of the prion protein already rely on monoclonal antibodies. Recombinant antibodies such as the single-chain Fv may soon replace traditional hybridoma techniques. Binding affinity can easily be manipulated by a number of techniques, including in vitro mutagenesis - a step which could never be carried out using the traditional hybridoma technology. Monoclonal antibodies are and will remain an essential support for ongoing research on the prion protein in general and on the unconventional infectious prions.

  17. Heterogeneity of monoclonal antibodies revealed by charge-sensitive methods.

    Science.gov (United States)

    Vlasak, J; Ionescu, R

    2008-12-01

    The expanding field of monoclonal antibody-based pharmaceuticals has triggered increased interest in analytical characterization of these large proteins and in understanding of their heterogeneity and degradation pathways. As a result, a large number of enzymatic modifications as well as chemical and physical degradations have been reported in monoclonal antibodies in recent years. Most heterogeneity is related to changes in the surface charge of the antibody, either directly, as a change in the number of charged residues, or indirectly as a chemical or physical alteration that changes surface-charge distribution. This review presents an overview of the sources of charge-related heterogeneity in monoclonal antibodies and the methods used for their detection. A detailed section is dedicated to deamidation of asparagine and isomerization of aspartic acid residues, two ubiquitous degradation pathways detected in antibodies and other proteins as well. Finally, kinetic modeling of the accumulation of antibody variants is presented as a tool to determine the expected fraction of molecules that have undergone one or more degradation reactions.

  18. [Single B cell monoclonal antibody technologies and applications].

    Science.gov (United States)

    Chi, Xiangyang; Yu, Changming; Chen, Wei

    2012-06-01

    Monoclonal antibodies (mAbs) contribute a lot to the development of numerous fields in life science as a pivotal tool in modern biological research. Development of the PCR methods and maturation of antibody production have made it possible to generate mAbs from single human B cells by single cell RT-PCR with successional cloning and expression in vitro. Compared to traditional monoclonal antibody technologies, single B cell technologies require relatively fewer cells, which are highly efficient in obtaining specific mAbs in a rapid way with preservation of the natural heavy and light chain pairing. With so many advantages, single B cell technologies have been proved to be an attractive approach for retrieval of naive and antigen-experienced antibody repertoires generated in vivo, design of rationale structure-based vaccine, evaluation and development of basic B cell biology concepts in health and autoimmunity, and prevention of infectious diseases by passive immunization and therapy for disorders. Accordingly, this review introduced recent progresses in the single B cell technologies for generating monoclonal antibodies and applications.

  19. Library of monoclonal antibodies against brush border membrane epithelial antigens

    Energy Technology Data Exchange (ETDEWEB)

    Behar, M.; Katz, A.; Silverman, M.

    1986-03-01

    A purified fraction of proximal tubule brush border membranes (BBM) was prepared from dog kidney and used to immunize mice. The standard technique of hybridoma production was followed as described by Kohler and Milstein. Production of antibodies was detected by indirect immunofluorescence on dog kidney slices and by immunodot against the purified fraction on nitrocellulose. Five hybrids exhibited anti BBM activity. These were cloned twice and yielded stable cell lines producing IgG type monoclonal antibodies against BBM. They were designated A/sub 1/, C/sub 7/, D/sub 3/, D/sub 7/ and H/sub 4/. As a family these five monoclonals have broad tissue specificity, i.e. positive staining of the surface mucosa of intestinal kidney proximal tubules. D/sub 3/ exhibits even broader specificity for epithelium reacting with bile canaliculi and choroid plexus. The authors have verified that at least 4/5 antibodies are directed against BBM protein as revealed by immunoprecipitation of solubilized BBM and detected by Coomassie blue staining or autoradiography of lactoperoxidase labelled BBM. Most interestingly all antibodies bind to the surface of LL CPK/sub 1/ cells, a continuous pig kidney cell line of undefined origin but exhibiting many characteristics of proximal tubule cells. The library of monoclonal antibodies obtained provide important probes with which to study membrane biogenesis and polarization in epithelial cells.

  20. Smart Substitutions for Healthy Cooking

    Science.gov (United States)

    ... Recognition & Awards Healthy Workplace Food and Beverage Toolkit Smart Substitutions Updated:Dec 16,2016 Healthy eating doesn’ ... mean giving up all the foods you love! Smart substitutions can help you maintain an overall healthy ...

  1. National Center for Healthy Housing

    Science.gov (United States)

    ... Resources Search NCHH Resources Ask NCHH Blog Building Materials and Products Consumer Survey Healthcare Financing How Can We Help You? Additional Resources Healthy Housing Clearinghouse Healthy Housing Links Healthy Housing Videos Lead ...

  2. Healthy habits for weight loss

    Science.gov (United States)

    ... gov/ency/patientinstructions/000733.htm Healthy habits for weight loss To use the sharing features on this page, ... to think about it. People who succeed at weight loss, turn healthy eating into a habit. These healthy ...

  3. [Detection of Helicobacter pylori in children and adolescents using the monoclonal coproantigen immunoassay and its association with gastrointestinal diseases].

    Science.gov (United States)

    Castillo-Montoya, Verónica; Ruiz-Bustos, Eduardo; Valencia-Juillerat, Mauro Eduardo; Álvarez-Hernández, Gerardo; Sotelo-Cruz, Norberto

    Infection by Helicobacter pylori (H. pilory) affects 50% of the world population. Simple methods for its detection are now available. To identify H. pylori by using a monoclonal coproantigen technique in paediatric patients, and to determine its association with gastrointestinal diseases. The study included a total of 110 subjects aged 1 to 18 years. The study variables included: Family history of gastrointestinal disease, age, gender, gastrointestinal symptoms, as well as apparently healthy (asymptomatic) subjects. The monoclonal coproantigen test was performed on stool samples. Two groups, I symptomatic (n=29), and II asymptomatic (n=81) were compared using parametric and non-parametric statistics. Of the 110 patients, 59 (54%) were male. The relationship between a family history of gastritis and a positive for H. pylori, was significant for mothers (pH. pylori and various signs and symptoms, such as epigastric pain (pH. pylori detection, was positive in 28% of both groups, and showed significant relationships with family gastrointestinal diseases and gastrointestinal symptoms. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  4. Characterization of equine vitamin D–binding protein, development of an assay, and assessment of plasma concentrations of the protein in healthy horses and horses with gastrointestinal disease

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Jacobsen, Stine; Olsen, Dorthe T.

    2017-01-01

    spectrometry. Monoclonal and polyclonal antibodies were raised against equine VDBP, and a rocket immunoelectrophoresis assay for equine VDBP was established. Plasma samples from 61 healthy horses were used to establish working VDBP reference values for study purposes. Plasma VDBP concentrations were assessed...

  5. A Healthy Person

    Science.gov (United States)

    Høye, Sevald; Kvigne, Kari; Aiyub, Ilyas; Gillund, Margrethe V.; Hermansyah, Hasan; Nordström, Gun; Rystedt, Ingrid; Suwarni, Abubakar; Trollvik, Anne; Wilde-Larsson, Bodil; Hov, Reidun

    2016-01-01

    The purpose of this exploratory study was to investigate how nursing students in Indonesia and Scandinavia characterize a healthy person. Two hundred thirty-two nursing students from Indonesia, 50 students from Sweden, and 119 students from Norway participated by answering an open-ended question. Qualitative content analysis was used to identify patterns of health in a cultural and national context. The characteristics of a healthy person were summarized in the theme “external and inner balance,” which are intertwined because of the wholeness of self-image and appearance. The subcategories were having a strong and positive body image, feeling well and having inner harmony, following the rules of life, coping with challenges, and acting in unison with the environment. There were more similarities than differences between the Indonesian and Scandinavian nursing students’ understanding of being a healthy person. The difference is that the Scandinavian students mentioned individuality, whereas the Indonesian students referred to collective values. PMID:28462342

  6. Improved detection of Pneumocystis carinii by an immunofluorescence technique using monoclonal antibodies

    DEFF Research Database (Denmark)

    Orholm, M; Holten-Andersen, W; Lundgren, Jens Dilling

    1990-01-01

    To assess whether a recently developed indirect immunofluorescent stain using monoclonal antibodies was more sensitive in detecting Pneumocystis carinii than the combination of Giemsa and methenamine silver nitrate stains which has routinely been used in the laboratory, 88 lavage fluid specimens...... and 34 induced sputum specimens were examined. All specimens were stained by five techniques: immunofluorescence using a combination of three monoclonal antibodies (from the National Institutes of Health, USA), immunofluorescence using a single monoclonal antibody (from Dakopatts), Giemsa, methenamine...

  7. High-efficiency screening of monoclonal antibodies for membrane protein crystallography.

    Directory of Open Access Journals (Sweden)

    Hyun-Ho Lim

    Full Text Available Determination of crystal structures of membrane proteins is often limited by difficulties obtaining crystals diffracting to high resolution. Co-crystallization with Fab fragments of monoclonal antibodies has been reported to improve diffraction of membrane proteins crystals. However, it is not simple to generate useful monoclonal antibodies for membrane protein crystallography. In this report, we present an optimized process for efficient screening from immunization to final validation of monoclonal antibody for membrane protein crystallography.

  8. In-vitro inhibition of IFNγ+ iTreg mediated by monoclonal antibodies against cell surface determinants essential for iTreg function

    OpenAIRE

    Daniel Volker; Sadeghi Mahmoud; Wang Haihao; Opelz Gerhard

    2012-01-01

    Abstract Background IFNγ-producing CD4+CD25+Foxp3+ PBL represent a subtype of iTreg that are associated with good long-term graft outcome in renal transplant recipients and suppress alloresponses in-vitro. To study the mechanism of immunosuppression, we attempted to block cell surface receptors and thereby inhibited the function of this iTreg subset in-vitro using monoclonal antibodies and recombinant proteins. Methods PBL of healthy control individuals were stimulated polyclonally in-vitro i...

  9. Production and Characterization of Monoclonal Antibodies of Shrimp White Spot Syndrome Virus Envelope Protein VP28

    Institute of Scientific and Technical Information of China (English)

    Wan-gang GU; Jun-fa YUAN; Ge-lin XU; Li-juan LI; Ni LIU; Cong ZHANG; Jian-hong ZHANG; Zheng-li SHI

    2007-01-01

    BALB/c mice were immunized with purified White spot syndrome virus (WSSV).Six monoclonal antibody cell lines were selected by ELISA with VP28 protein expressed in E.coll in vitro neutralization experiments showed that 4 of them could inhibit the virus infection in crayfish.Westernblot suggested that all these monoclonal antibodies were against the conformational structure of VP28.The monoclonal antibody 7B4 was labeled with colloidal gold particles and used to locate the VP28 on virus envelope by immunogold labeling.These monoclonal antibodies could be used to develop immunological diagnosis methods for WSSV infection.

  10. Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.

    Science.gov (United States)

    Hauswirth, Alexander W; Almeida, Julia; Nieto, Wendy G; Teodosio, Cristina; Rodriguez-Caballero, Arancha; Romero, Alfonso; López, Antonio; Fernandez-Navarro, Paulino; Vega, Tomas; Perez-Andres, Martin; Valent, Peter; Jäger, Ulrich; Orfao, Alberto

    2012-07-01

    Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal B-cell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naive B-cells; in addition, CD4+CD8+ double-positive T-cells and CD8+ T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at >1% MBL-counts, vs. "low-count" MBL cases, and lower amounts of immature/naive B-cells were detected in biclonal (particularly in cases with coexisting CLL-like- and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and naıve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.

  11. Rheumatoid factor interference in immunogenicity assays for human monoclonal antibody therapeutics.

    Science.gov (United States)

    Tatarewicz, Suzanna; Miller, Jill M; Swanson, Steven J; Moxness, Michael S

    2010-05-31

    Rheumatoid factors (RFs) are endogenous human antibodies that bind to human gamma globulins. RFs demonstrate preferential binding to aggregated gamma globulins and are involved in the clearing mechanism of immune complexes. Immunoassays designed to measure human anti-human antibodies (HAHA) after administration of monoclonal antibody therapeutics are thus vulnerable to interference from RFs. When using a sensitive electrochemiluminescent (ECL) bridging immunoassay, samples from subjects with rheumatoid arthritis demonstrated much higher baseline reactivity than healthy subjects. Interference was found to be dependent on the aggregation state of the therapeutic antibody that had been conjugated with the detection reagent (ruthenium). Size exclusion high performance liquid chromatography (SE-HPLC) demonstrated that of the total integrated peaks, as little as 0.55% high molecular weight aggregates (>600kDa) were sufficient to cause increased reactivity. Stability studies of the ruthenium and biotin conjugated therapeutic antibody indicated that storage time, temperature and buffer formulation were critical in maintaining the integrity of the reagents. Through careful SE-HPLC monitoring we were able to choose appropriate storage and buffer conditions which led to a reduction in the false reactivity rate in therapeutic-naïve serum from a rheumatoid arthritis population.

  12. In Vitro Characterization of Human Cytomegalovirus-Targeting Therapeutic Monoclonal Antibodies LJP538 and LJP539

    Science.gov (United States)

    Patel, Hetalkumar D.; Nikitin, Pavel; Gesner, Thomas; Lin, James J.; Barkan, David T.; Ciferri, Claudio; Carfi, Andrea; Akbarnejad Yazdi, Tahmineh; Skewes-Cox, Peter; Wiedmann, Brigitte; Jarousse, Nadine; Zhong, Weidong; Feire, Adam

    2016-01-01

    Human cytomegalovirus (HCMV) infection is usually benign in healthy individuals but can cause life-threatening disease in those with compromised immune systems. Approved drugs available to treat HCMV disease, including ganciclovir, cidofovir, and foscarnet, have significant toxicities that limit their use in certain patient populations. LJP538 and LJP539 are human monoclonal antibodies that are being evaluated as immunoglobulin therapeutics. The antibodies target glycoproteins gB and the gH/gL/UL128/UL130/UL131a pentameric complex, respectively. Here we present an in vitro characterization of these antibodies. We show that LJP538 and LJP539 are more potent than a marketed immunoglobulin at inhibiting HCMV infection of various cell lines relevant to pathogenesis. We find that LJP538 and LJP539 are active against a panel of clinical isolates in vitro and demonstrate minor-to-moderate synergy in combination. Passage of HCMV in the presence of LJP538 or LJP539 alone resulted in resistance-associated mutations that mapped to the target genes. However, no loss of susceptibility to the combination of antibodies was observed for >400 days in culture. Finally, the binding regions of LJP538 and LJP539 are conserved among clinical isolates. Taken together, these data support the use of LJP538 and LJP539 in combination for clinical trials in HCMV patients. PMID:27270290

  13. First-in-Man Study With Inclacumab, a Human Monoclonal Antibody Against P-selectin.

    Science.gov (United States)

    Schmitt, Christophe; Abt, Markus; Ciorciaro, Cornelia; Kling, Dorothee; Jamois, Candice; Schick, Eginhard; Solier, Corinne; Benghozi, Renée; Gaudreault, Jacques

    2015-06-01

    Inclacumab, a novel monoclonal antibody against P-selectin in development for the treatment and prevention of atherosclerotic cardiovascular diseases, was administered in an ascending single-dose study as intravenous infusion to evaluate safety, pharmacokinetics, and pharmacodynamics. Fifty-six healthy subjects were enrolled in this randomized, double-blind placebo-controlled study. Each dose level (0.03-20 mg/kg) was investigated in separate groups of 8 subjects (6 on inclacumab, 2 on placebo). Platelet-leukocyte aggregates, free/total soluble P-selectin concentration ratio, drug concentrations, bleeding time, platelet aggregation, antibody formation, and routine laboratory parameters were measured frequently until 32 weeks. Pharmacokinetic profiles were indicative of target-mediated drug disposition. Platelet-leukocyte aggregate inhibition and soluble P-selectin occupancy showed dose dependency and were strongly correlated to inclacumab plasma concentrations, with IC50 of 740 and 4600 ng/mL, respectively. Inclacumab was well tolerated by the majority of subjects and did neither affect bleeding time nor platelet aggregation. These findings allowed the investigation of the potential beneficial therapeutic use of inclacumab in patient study.

  14. Healthy Drinks for Kids

    Science.gov (United States)

    ... For Kids For Parents MORE ON THIS TOPIC Caffeine Calcium Sports and Energy Drinks: Should Your Child Drink Them? What Should Preschoolers ... Why Drinking Water Is the Way to Go Caffeine Confusion What's a Healthy Alternative to Water? Energy Drinks and Food Bars: Power or Hype? A Guide ...

  15. Getting Healthy Scientifically

    Institute of Scientific and Technical Information of China (English)

    Zhao Zhixin

    2010-01-01

    @@ Recently, Zhao Zhixin, a Beijing-based instructor on scientific bodybuiiding and public sport,was interviewed by China Youth Daily, sharing his views on how to get healthy scientifically.Edited excerpts follow: China Youth Daily: What do you think about food therapy as a regimen?

  16. Tips for Healthy Voices

    Science.gov (United States)

    ... social interaction as well as for most people’s occupation. Proper care and use of your voice will give you the best chance for having a healthy voice for your entire lifetime. Hoarseness or roughness in your voice is often ...

  17. Some like it healthy

    DEFF Research Database (Denmark)

    Contini, Caterina; Casini, Leonardo; Stancu, Violeta

    2015-01-01

    Authorising new health claims in Europe will favour the diffusion on the market of a greater number of foods with health claims. This scenario presents new opportunities to promote healthy food choices and launches new challenges to define strategies aimed at promoting products on the market. The...

  18. The Healthy Eating Pyramid

    Institute of Scientific and Technical Information of China (English)

    Jimmy; Lin

    2007-01-01

    Experts from the Harvard School of Public Health created the Healthy Eating Pyramid.The pyramid is about the links between diet and health and offers useable information to help people make better choices about what to eat. Remember:its base is daily exercise and weight control.

  19. Making Healthy Sexual Decisions

    Science.gov (United States)

    ... including your partner) ? Is your decision to have sex based on the right reasons? (It shouldn’t be based on peer ... re ready! Tags: birth control , condoms , contraception , healthy sex , peer ... Contraception (EC) Sexual Orientation and Gender Identity: General Information How do I ...

  20. Monitoring monoclonal antibody delivery in oncology: the example of bevacizumab.

    Directory of Open Access Journals (Sweden)

    Guillaume Nugue

    Full Text Available Developing therapeutic monoclonal antibodies paves the way for new strategies in oncology using targeted therapy which should improve specificity. However, due to a lack of biomarkers, a personalized therapy scheme cannot always be applied with monoclonal antibodies. As a consequence, the efficacy or side effects associated with this type of treatment often appear to be sporadic. Bevacizumab is a therapeutic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF. It is used to limit tumor vascularization. No prognosis or response biomarker is associated with this antibody, we therefore assessed whether the administration protocol could be a possible cause of heterogeneous responses (or variable efficacy. To do this, we developed a bevacizumab assay with a broad sensitivity range to measure blood bevacizumab concentrations. We then analyzed bevacizumab concentrations in 17 patients throughout the first quarter of treatment. In line with previously published data, average blood concentrations were 88+/-27 mg/L following the first dose administered, and 213+/-105 mg/L after the last (6(th dose administered. However, the individual values were scattered, with a mean 4-fold difference between the lowest and the highest concentration for each dose administered. We demonstrated that the bevacizumab administration schedule results in a high inter-individual variability in terms of blood concentrations. Comparison of assay data with clinical data indicates that blood concentrations above the median are associated with side effects, whereas values below the median favor inefficacy. In conclusion, bevacizumab-based therapy could benefit from a personalized administration schedule including follow-up and adjustment of circulating bevacizumab concentrations.

  1. Monoclonal IgA Antibodies for Aflatoxin Immunoassays

    Directory of Open Access Journals (Sweden)

    Özlem Ertekin

    2016-05-01

    Full Text Available Antibody based techniques are widely used for the detection of aflatoxins which are potent toxins with a high rate of occurrence in many crops. We developed a murine monoclonal antibody of immunoglobulin A (IgA isotype with a strong binding affinity to aflatoxin B1 (AFB1, aflatoxin B2 (AFB2, aflatoxin G1 (AFG1, aflatoxin G2 (AFG2 and aflatoxin M1 (AFM1. The antibody was effectively used in immunoaffinity column (IAC and ELISA kit development. The performance of the IACs was compatible with AOAC performance standards for affinity columns (Test Method: AOAC 991.31. The total binding capacity of the IACs containing our antibody was 111 ng, 70 ng, 114 ng and 73 ng for AFB1, AFB2, and AFG1 andAFG2, respectively. Furthermore, the recovery rates of 5 ng of each AF derivative loaded to the IACs were determined as 104.9%, 82.4%, 85.5% and 70.7% for AFB1, AFB2, AFG1 and AFG2, respectively. As for the ELISA kit developed using non-oriented, purified IgA antibody, we observed a detection range of 2–50 µg/L with 40 min total test time. The monoclonal antibody developed in this research is hitherto the first presentation of quadruple antigen binding IgA monoclonal antibodies in mycotoxin analysis and also the first study of their utilization in ELISA and IACs. IgA antibodies are valuable alternatives for immunoassay development, in terms of both sensitivity and ease of preparation, since they do not require any orientation effort.

  2. The use of combinations of monoclonal antibodies in clinical oncology.

    Science.gov (United States)

    Henricks, Linda M; Schellens, Jan H M; Huitema, Alwin D R; Beijnen, Jos H

    2015-12-01

    Treatment with monoclonal antibodies is becoming increasingly important in clinical oncology. These antibodies specifically inhibit signaling pathways in tumor growth and/or induce immunological responses against tumor cells. By combining monoclonal antibodies several pathways may be targeted simultaneously, potentially leading to additive or synergistic effects. Theoretically, antibodies are very suitable for use in combination therapy, because of limited overlapping toxicity and lack of pharmacokinetic interactions. In this article an overview is given of preclinical and clinical data on twenty-five different combinations of antibodies in oncology. Some of these combinations have proven clinical benefit, for example the combination of trastuzumab and pertuzumab in HER2-positive breast cancer, which exemplifies an additive or synergistic effect on antitumor activity in clinical studies and the combination of nivolumab and ipilimumab, which results in significant increases in progression-free and overall survival in patients with advanced melanoma. However, other combinations may lead to unfavorable results, such as bevacizumab with cetuximab or panitumumab in advanced colorectal cancer. These combinations result in shorter progression-free survival and increased toxicity compared to therapy with a single antibody. In summary, the different published studies showed widely varying results, depending on the combination of antibodies, indication and patient population. More preclinical and clinical studies are necessary to unravel the mechanisms behind synergistic or antagonistic effects of combining monoclonal antibodies. Most research on combination therapies is still in an early stage, but it is expected that for several tumor types the use of combination therapy of antibodies will become standard of care in the near future.

  3. Monoclonal IgA Antibodies for Aflatoxin Immunoassays

    Science.gov (United States)

    Ertekin, Özlem; Pirinçci, Şerife Şeyda; Öztürk, Selma

    2016-01-01

    Antibody based techniques are widely used for the detection of aflatoxins which are potent toxins with a high rate of occurrence in many crops. We developed a murine monoclonal antibody of immunoglobulin A (IgA) isotype with a strong binding affinity to aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2) and aflatoxin M1 (AFM1). The antibody was effectively used in immunoaffinity column (IAC) and ELISA kit development. The performance of the IACs was compatible with AOAC performance standards for affinity columns (Test Method: AOAC 991.31). The total binding capacity of the IACs containing our antibody was 111 ng, 70 ng, 114 ng and 73 ng for AFB1, AFB2, and AFG1 andAFG2, respectively. Furthermore, the recovery rates of 5 ng of each AF derivative loaded to the IACs were determined as 104.9%, 82.4%, 85.5% and 70.7% for AFB1, AFB2, AFG1 and AFG2, respectively. As for the ELISA kit developed using non-oriented, purified IgA antibody, we observed a detection range of 2–50 µg/L with 40 min total test time. The monoclonal antibody developed in this research is hitherto the first presentation of quadruple antigen binding IgA monoclonal antibodies in mycotoxin analysis and also the first study of their utilization in ELISA and IACs. IgA antibodies are valuable alternatives for immunoassay development, in terms of both sensitivity and ease of preparation, since they do not require any orientation effort. PMID:27187470

  4. Monoclonal IgA Antibodies for Aflatoxin Immunoassays.

    Science.gov (United States)

    Ertekin, Özlem; Pirinçci, Şerife Şeyda; Öztürk, Selma

    2016-05-12

    Antibody based techniques are widely used for the detection of aflatoxins which are potent toxins with a high rate of occurrence in many crops. We developed a murine monoclonal antibody of immunoglobulin A (IgA) isotype with a strong binding affinity to aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2) and aflatoxin M1 (AFM1). The antibody was effectively used in immunoaffinity column (IAC) and ELISA kit development. The performance of the IACs was compatible with AOAC performance standards for affinity columns (Test Method: AOAC 991.31). The total binding capacity of the IACs containing our antibody was 111 ng, 70 ng, 114 ng and 73 ng for AFB1, AFB2, and AFG1 andAFG2, respectively. Furthermore, the recovery rates of 5 ng of each AF derivative loaded to the IACs were determined as 104.9%, 82.4%, 85.5% and 70.7% for AFB1, AFB2, AFG1 and AFG2, respectively. As for the ELISA kit developed using non-oriented, purified IgA antibody, we observed a detection range of 2-50 µg/L with 40 min total test time. The monoclonal antibody developed in this research is hitherto the first presentation of quadruple antigen binding IgA monoclonal antibodies in mycotoxin analysis and also the first study of their utilization in ELISA and IACs. IgA antibodies are valuable alternatives for immunoassay development, in terms of both sensitivity and ease of preparation, since they do not require any orientation effort.

  5. Alemtuzumab and Natalizumab: The Monoclonal Antibody Story Continues

    Directory of Open Access Journals (Sweden)

    BL Johnston

    2006-01-01

    Full Text Available In the July/August 2006 issue of this journal, the infectious complications associated with the use of infliximab, etanercept and adalimumab were reviewed (1. These represent only three of the many monoclonal antibodies either licensed or in clinical trials for therapeutic use in cancer and autoimmune disease or to prevent rejection in both solid organ and hematopoietic stem cell transplantation. While most of these agents have not been associated with increased infection rates, alemtuzumab and natalizumab have gained particular attention related to either the frequency or type of infection seen in some individuals who have received them.

  6. Monoclonal IgA Antibodies for Aflatoxin Immunoassays

    OpenAIRE

    2016-01-01

    Antibody based techniques are widely used for the detection of aflatoxins which are potent toxins with a high rate of occurrence in many crops. We developed a murine monoclonal antibody of immunoglobulin A (IgA) isotype with a strong binding affinity to aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2) and aflatoxin M1 (AFM1). The antibody was effectively used in immunoaffinity column (IAC) and ELISA kit development. The performance of the IACs was compatible ...

  7. Rapid analysis of small samples containing forskolin using monoclonal antibodies.

    Science.gov (United States)

    Yanagihara, H; Sakata, R; Shoyama, Y; Murakami, H

    1996-04-01

    The effective range of the competitive ELISA test for detection of forskolin content in clonally propagated plant organs of Coleus forskohlii using monoclonal antibodies extends from 5ng to 5 micrograms. A correlation between the forskolin accumulation and the growth rate was investigated using the clonally propagated shoots. An increase of forskolin content was noted, beginning at week 6. Flowers, rachises, leaves, stems, tuberous roots, and roots were analyzed. Tuberous roots and the stem base contained higher amounts of forskolin than other organs. The forskolin content in the stem decreased gradually towards the top of the shoot.

  8. Fluorescence polarization immunoassay for salinomycin based on monoclonal antibodies

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A fluorescence polarization immunoassay(FPIA) for the determination of salinomycin(SAL) was developed by using anti-SAL monoclonal antibodies(mAb).Fluorescein labeled SAL(tracer) was synthesized by the N-hydroxysuccinimide active ester method and purified using thin layer chromatography(TLC).The developed FPIA for SAL had a dynamic range from 0.60 to 2193 ng/mL with an IC50 value of 33.2 ng/mL and a detection limit(LOD) of 0.08 ng/mL.No significant cross-reactivities were observed with other drugs but 67.6% with narasin.

  9. Monoclonal antibody therapy in the treatment of Reye's syndrome.

    Science.gov (United States)

    Treon, S P; Broitman, S A

    1992-11-01

    A role for lipopolysaccharides (endotoxins, LPS) in 7 the pathogenesis of Reye's syndrome (RS) has previously been suggested. Impairment of hepatic LPS clearance can lead to systemic endotoxemia as previous studies by this and other laboratories have suggested for several hepatic disorders including RS. Systemic LPS may mediate many of the clinical findings associated with RS by eliciting monokines such as tumor necrosis factor-alpha, interleukin-1, interleukin-6, and interleukin-8. Monoclonal antibody therapy directed at LPS, and monokines may represent a novel approach to the treatment of RS.

  10. Large-scale production of monoclonal antibodies in suspension culture.

    Science.gov (United States)

    Backer, M P; Metzger, L S; Slaber, P L; Nevitt, K L; Boder, G B

    1988-10-01

    Monoclonal antibodies are being manufactured for clinical trials in suspension culture at the 1300-L scale. Suspension culture offers some advantages relative to high-density mammalian cell culture methods; in particular, the ability to closely monitor the behavior of cells in a homogeneous environment. Computer control and on-line mass spectrography of exit gases provide instantaneous information about the culture metabolic activity. Air sparging and agitation by marine impeller provide aeration sufficient to maintain a constant dissolved oxygen tension at cell concentrations up to 5.0 x 10(6) cells/mL without causing apparent cell damage.

  11. Monoclonal Antibodies as Prophylactic and Therapeutic Agents Against Chikungunya Virus.

    Science.gov (United States)

    Clayton, April M

    2016-12-15

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for considerable epidemics worldwide and recently emerged in the Americas in 2013. CHIKV may cause long-lasting arthralgia after acute infection. With currently no licensed vaccines or antivirals, the design of effective therapies to prevent or treat CHIKV infection is of utmost importance and will be facilitated by increased understanding of the dynamics of chikungunya. In this article, monoclonal antibodies against CHIKV as viable prophylactic and therapeutic agents will be discussed. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Inherited polymorphisms in hyaluronan synthase 1 predict risk of systemic B-cell malignancies but not of breast cancer.

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    Hemalatha Kuppusamy

    Full Text Available Genetic variations in the hyaluronan synthase 1 gene (HAS1 influence HAS1 aberrant splicing. HAS1 is aberrantly spliced in malignant cells from multiple myeloma (MM and Waldenstrom macroglobulinemia (WM, but not in their counterparts from healthy donors. The presence of aberrant HAS1 splice variants predicts for poor survival in multiple myeloma (MM. We evaluated the influence of inherited HAS1 single nucleotide polymorphisms (SNP on the risk of having a systemic B cell malignancy in 1414 individuals compromising 832 patients and 582 healthy controls, including familial analysis of an Icelandic kindred. We sequenced HAS1 gene segments from 181 patients with MM, 98 with monoclonal gammopathy of undetermined significance (MGUS, 72 with Waldenstrom macroglobulinemia (WM, 169 with chronic lymphocytic leukemia (CLL, as well as 34 members of a monoclonal gammopathy-prone Icelandic family, 212 age-matched healthy donors and a case-control cohort of 295 breast cancer patients with 353 healthy controls. Three linked single nucleotide polymorphisms (SNP in HAS1 intron3 are significantly associated with B-cell malignancies (range p = 0.007 to p = 10(-5, but not MGUS or breast cancer, and predict risk in a 34 member Icelandic family (p = 0.005, Odds Ratio = 5.8 (OR, a relatively homogeneous cohort. In contrast, exon3 SNPs were not significantly different among the study groups. Pooled analyses showed a strong association between the linked HAS1 intron3 SNPs and B-cell malignancies (OR = 1.78, but not for sporadic MGUS or for breast cancer (OR<1.0. The minor allele genotypes of HAS1 SNPs are significantly more frequent in MM, WM, CLL and in affected members of a monoclonal gammopathy-prone family than they are in breast cancer, sporadic MGUS or healthy donors. These inherited changes may increase the risk for systemic B-cell malignancies but not for solid tumors.

  13. Production of Monoclonal Antibody Against Excretory-Secretory Antigen of Fasciola hepatica and Evaluation of Its Efficacy in the Diagnosis of Fascioliasis.

    Science.gov (United States)

    Abdolahi Khabisi, Samaneh; Sarkari, Bahador; Moshfe, Abdolali; Jalali, Sedigheh

    2017-02-01

    Parasitological methods are not helpful for the diagnosis of fascioliasis in acute and invasive periods of the disease. Detection of coproantigens seems to be a suitable alternative approach in the diagnosis of fascioliasis. The present study aimed to develop a reliable antigen detection system, using monoclonal antibodies raised against excretory-secretory (ES) antigen of Fasciola hepatica, for the diagnosis of fascioliasis. Fasciola adult worms were collected from the bile ducts of infected animals. Species of the fluke was determined by polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR). ES antigen of F. hepatica was prepared. For production of monoclonal antibodies, mice were immunized with ES antigens of F. hepatica. Spleen cells from the immunized mice were fused with NS-1 myeloma cells, using polyethylene glycol. Hybridoma cells secreting specific antibody were expanded and cloned by limiting dilution. Moreover, polyclonal antibody was produced against F. hepatica ES antigen in rabbits. A capture enzyme-linked immunosorbent assay (ELISA) system, using produced monoclonal antibody, was designed and stool samples of infected animals along with control samples were tested by the system. The capture ELISA detected the coproantigen in 27 of 30 (90%) parasitologically confirmed fascioliasis cases, while 4 of 39 (10.25%) samples infected with other parasitic infections showed a positive reaction in this system. No positive reactivity was found with healthy control samples. Accordingly, sensitivity of 90% and specificity of 94.2% were obtained for the capture ELISA system. The results were compared with those obtained with commercial BIO-X ELISA, and a very good (kappa = 0.9) agreement was found between the commercial kit and the developed capture ELISA. Findings of this study showed that the produced monoclonal antibody has appropriate performance for the detection of Fasciola coproantigen in stool samples and can be appropriately

  14. Antibody-Dependent Cell-Mediated Cytotoxicity Effector-Enhanced EphA2 Agonist Monoclonal Antibody Demonstrates Potent Activity against Human Tumors

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Bruckheimer

    2009-06-01

    Full Text Available EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vitro and in vivo antibody-dependent cell-mediated cytotoxicity (ADCC activity of EphA2 effector-enhanced agonist monoclonal antibodies was evaluated. With tumor cell lines and healthy human peripheral blood monocytes, the EphA2 antibodies demonstrated ∼80% tumor cell killing. In a dose-dependent manner, natural killer (NK cells were required for the in vitro ADCC activity and became activated as demonstrated by the induction of cell surface expression of CD107a. To assess the role of NK cells on antitumor efficacy in vivo, the EphA2 antibodies were evaluated in xenograft models in severe compromised immunodeficient (SCID mice (which have functional NK cells and monocytes and SCID nonobese diabetic (NOD mice (which largely lack functional NK cells and monocytes. Dosing of EphA2 antibody in the SCID murine tumor model resulted in a 6.2-fold reduction in tumor volume, whereas the SCID/nonobese diabetic model showed a 1.6-fold reduction over the isotype controls. Together, these results demonstrate that the anti-EphA2 monoclonal antibodies may function through at least two mechanisms of action: EphA2 receptor activation and ADCC-mediated activity. These novel EphA2 monoclonal antibodies provide additional means by which host effector mechanisms can be activated for selective destruction of EphA2-expressing tumor cells.

  15. Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants.

    Science.gov (United States)

    Ma, Julian K-C; Drossard, Jürgen; Lewis, David; Altmann, Friedrich; Boyle, Julia; Christou, Paul; Cole, Tom; Dale, Philip; van Dolleweerd, Craig J; Isitt, Valerie; Katinger, Dietmar; Lobedan, Martin; Mertens, Hubert; Paul, Mathew J; Rademacher, Thomas; Sack, Markus; Hundleby, Penelope A C; Stiegler, Gabriela; Stoger, Eva; Twyman, Richard M; Vcelar, Brigitta; Fischer, Rainer

    2015-10-01

    Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins. © 2015 Society for Experimental Biology, Association of

  16. Membrane adsorbers as purification tools for monoclonal antibody purification.

    Science.gov (United States)

    Boi, Cristiana

    2007-03-15

    Downstream purification processes for monoclonal antibody production typically involve multiple steps; some of them are conventionally performed by bead-based column chromatography. Affinity chromatography with Protein A is the most selective method for protein purification and is conventionally used for the initial capturing step to facilitate rapid volume reduction as well as separation of the antibody. However, conventional affinity chromatography has some limitations that are inherent with the method, it exhibits slow intraparticle diffusion and high pressure drop within the column. Membrane-based separation processes can be used in order to overcome these mass transfer limitations. The ligand is immobilized in the membrane pores and the convective flow brings the solute molecules very close to the ligand and hence minimizes the diffusional limitations associated with the beads. Nonetheless, the adoption of this technology has been slow because membrane chromatography has been limited by a lower binding capacity than that of conventional columns, even though the high flux advantages provided by membrane adsorbers would lead to higher productivity. This review considers the use of membrane adsorbers as an alternative technology for capture and polishing steps for the purification of monoclonal antibodies. Promising industrial applications as well as new trends in research will be addressed.

  17. Ofatumumab: a novel monoclonal anti-CD20 antibody

    Directory of Open Access Journals (Sweden)

    Thomas S Lin

    2010-05-01

    Full Text Available Thomas S LinGlaxoSmithKline Oncology R&D, Collegeville, PA, USAAbstract: Ofatumumab, a novel humanized monoclonal anti-CD20 antibody, was recently approved by the FDA for the treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL. Ofatumumab effectively induces complement-dependent cytotoxicity (CDC in vitro, and recent studies demonstrated that ofatumumab also effectively mediates antibody-dependent cellular cytotoxicity (ADCC. Pharmacokinetic studies indicated that increased exposure to the antibody correlated with improved clinical outcome in CLL. Thus, pharmacogenomics may be important in identifying which patients are more likely to respond to ofatumumab therapy, although such studies have not yet been performed. Patients with the high-affinity FCGR3a 158 V/V polymorphism may be more likely to respond to therapy, if ADCC is the primary in vivo mechanism of action of ofatumumab. Patients with increased expression of the complement defense proteins CD55 and CD59 may be less likely to respond if ofatumumab works in vivo primarily via CDC. Patients with increased metabolism and clearance of ofatumumab may have lower exposure and be less likely to respond clinically. Thus, pharmacogenomics may determine the responsiveness of patients to ofatumumab therapy.Keywords: monoclonal antibody, CD20, CLL, NHL, lymphoma

  18. Monoclonal Antibody Therapy and Renal Transplantation: Focus on Adverse Effects

    Directory of Open Access Journals (Sweden)

    Gianluigi Zaza

    2014-02-01

    Full Text Available A series of monoclonal antibodies (mAbs are commonly utilized in renal transplantation as induction therapy (a period of intense immunosuppression immediately before and following the implant of the allograft, to treat steroid-resistant acute rejections, to decrease the incidence and mitigate effects of delayed graft function, and to allow immunosuppressive minimization. Additionally, in the last few years, their use has been proposed for the treatment of chronic antibody-mediated rejection, a major cause of late renal allograft loss. Although the exact mechanism of immunosuppression and allograft tolerance with any of the currently used induction agents is not completely defined, the majority of these medications are targeted against specific CD proteins on the T or B cells surface (e.g., CD3, CD25, CD52. Moreover, some of them have different mechanisms of action. In particular, eculizumab, interrupting the complement pathway, is a new promising treatment tool for acute graft complications and for post-transplant hemolytic uremic syndrome. While it is clear their utility in renal transplantation, it is also unquestionable that by using these highly potent immunosuppressive agents, the body loses much of its innate ability to mount an adequate immune response, thereby increasing the risk of severe adverse effects (e.g., infections, malignancies, haematological complications. Therefore, it is extremely important for clinicians involved in renal transplantation to know the potential side effects of monoclonal antibodies in order to plan a correct therapeutic strategy minimizing/avoiding the onset and development of severe clinical complications.

  19. Monoclonal antibodies directed to fucoidan preparations from brown algae.

    Science.gov (United States)

    Torode, Thomas A; Marcus, Susan E; Jam, Murielle; Tonon, Thierry; Blackburn, Richard S; Hervé, Cécile; Knox, J Paul

    2015-01-01

    Cell walls of the brown algae contain a diverse range of polysaccharides with useful bioactivities. The precise structures of the sulfated fucan/fucoidan group of polysaccharides and their roles in generating cell wall architectures and cell properties are not known in detail. Four rat monoclonal antibodies, BAM1 to BAM4, directed to sulfated fucan preparations, have been generated and used to dissect the heterogeneity of brown algal cell wall polysaccharides. BAM1 and BAM4, respectively, bind to a non-sulfated epitope and a sulfated epitope present in the sulfated fucan preparations. BAM2 and BAM3 identified additional distinct epitopes present in the fucoidan preparations. All four epitopes, not yet fully characterised, occur widely within the major brown algal taxonomic groups and show divergent distribution patterns in tissues. The analysis of cell wall extractions and fluorescence imaging reveal differences in the occurrence of the BAM1 to BAM4 epitopes in various tissues of Fucus vesiculosus. In Ectocarpus subulatus, a species closely related to the brown algal model Ectocarpus siliculosus, the BAM4 sulfated epitope was modulated in relation to salinity levels. This new set of monoclonal antibodies will be useful for the dissection of the highly complex and yet poorly resolved sulfated polysaccharides in the brown algae in relation to their ecological and economic significance.

  20. Monoclonal antibodies directed to fucoidan preparations from brown algae.

    Directory of Open Access Journals (Sweden)

    Thomas A Torode

    Full Text Available Cell walls of the brown algae contain a diverse range of polysaccharides with useful bioactivities. The precise structures of the sulfated fucan/fucoidan group of polysaccharides and their roles in generating cell wall architectures and cell properties are not known in detail. Four rat monoclonal antibodies, BAM1 to BAM4, directed to sulfated fucan preparations, have been generated and used to dissect the heterogeneity of brown algal cell wall polysaccharides. BAM1 and BAM4, respectively, bind to a non-sulfated epitope and a sulfated epitope present in the sulfated fucan preparations. BAM2 and BAM3 identified additional distinct epitopes present in the fucoidan preparations. All four epitopes, not yet fully characterised, occur widely within the major brown algal taxonomic groups and show divergent distribution patterns in tissues. The analysis of cell wall extractions and fluorescence imaging reveal differences in the occurrence of the BAM1 to BAM4 epitopes in various tissues of Fucus vesiculosus. In Ectocarpus subulatus, a species closely related to the brown algal model Ectocarpus siliculosus, the BAM4 sulfated epitope was modulated in relation to salinity levels. This new set of monoclonal antibodies will be useful for the dissection of the highly complex and yet poorly resolved sulfated polysaccharides in the brown algae in relation to their ecological and economic significance.

  1. Monoclonal Antibody Production against Human Spermatozoal Surface Antigens

    Directory of Open Access Journals (Sweden)

    M Jedi-Tehrani

    2005-10-01

    Full Text Available Introduction: As monoclonal antibodies are potential tools for characterization of soluble or cellular surface antigens, use of these proteins has always been considered in infertility and reproduction research. Therefore, in this study, monoclonal antibodies against human sperm surface antigens were produced. Material and Methods: To produce specific clones against human sperm surface antigens, proteins were extracted using solubilization methods. Balb/c mice were immunized intraperitoneally with the proteins using complete Freund’s adjuvant in the first injection and incomplete Adjuvant in the following booster injections. Hybridoma cells producing ASA were cloned by limiting dilution. Results: Five stable ASA producing hybridoma clones were achieved and their antibody isotypes were determined by ELISA. All the isotypes were of IgG class. Their cross reactivity with rat and mice spermatozoa was examined but they did not have any cross reactivity. Conclusion: The produced antibodies can be used in further studies to characterize and evaluate each of the antigens present on human sperm surface and determining their role in fertilization.

  2. Fingerprinting of Natural Product by Eastern Blotting Using Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Hiroyuki Tanaka

    2012-01-01

    Full Text Available We succeeded in developing the fingerprint of natural product by eastern blotting using monoclonal antibodies. After developing and separating them on a TLC plate, solasodine glycosides are oxidized by NaIO4 and reacted with a protein to give conjugates which are recognized with anti-solamargine monoclonal antibody (MAb. Anti-solamargine MAb having wide cross-reactivity can stain and detect all solasodine glycosides by fingerprint. Different sensitivity between solamargine and solasonine was observed. The detection limit was 1.6 ng of solasonine. The hydrolysed products of solamargine were determined by fingerprint of eastern blotting compared to their Rf values depending on the sugar number. Fingerprint by eastern blotting using anti-ginsenoside Rb1 MAb distinguished the formula containing ginseng prescribed in traditional Chinese medicine. By double-staining of ginsenosides it is possible to suggest that the staining color shows the pharmacological activity, such as the purple bands indicate ginsenosides having stimulation activity, and the blue color indicated compound like ginsenosides possessed the depression affect for the central nervous system (CNS, respectively.

  3. Monoclonal Antibody-Based Therapeutics for Melioidosis and Glanders

    Directory of Open Access Journals (Sweden)

    Hyung-Yong Kim

    2011-01-01

    Full Text Available Problem statement: Burkholderia Pseudomallei (BP and B. Mallei (BM were two closely related pathogenic gram-negative bacteria. They were the causative agents of melioidosis and glanders, respectively and are recognized by CDC as category B select agents. Significant efforts had been devoted to developing the diagnostic and therapeutic measures against these two pathogens. Monoclonal antibody-based therapeutic was a promising targeted therapy to fight against melioidosis and glanders. Valuable findings have been reported by different groups in their attempt to identify vaccine targets against these two pathogens. Approach: Our group has generated neutralizing Monoclonal Antibodies (MAbs against BP and BM and characterized them by both in vitro and in vivo experiments. We present an overview of the MAb-based therapeutic approaches against BP and BM and demonstrate some of our efforts for developing chimeric and fully human MAbs using antibody engineering. Results: Throughout conventional mouse hybridoma technique and antibody engineering (chimerization and in vitro antibody library techniques, we generated 10 chimeric MAbs (3 stable MAbs and 7 transient MAbs and one fully human MAb against BP and BM. In addition, we present the reactive antigen profiles of these MAbs. Our approaches had potentials to accelerate the development of therapeutics for melioidosis and glanders in humans. Conclusion: Our experience and findings presented here will be valuable for choosing the best antigenic targets and ultimately for the production of effective vaccines for these two pathogens.

  4. Prediction and Reduction of the Aggregation of Monoclonal Antibodies.

    Science.gov (United States)

    van der Kant, Rob; Karow-Zwick, Anne R; Van Durme, Joost; Blech, Michaela; Gallardo, Rodrigo; Seeliger, Daniel; Aßfalg, Kerstin; Baatsen, Pieter; Compernolle, Griet; Gils, Ann; Studts, Joey M; Schulz, Patrick; Garidel, Patrick; Schymkowitz, Joost; Rousseau, Frederic

    2017-04-21

    Protein aggregation remains a major area of focus in the production of monoclonal antibodies. Improving the intrinsic properties of antibodies can improve manufacturability, attrition rates, safety, formulation, titers, immunogenicity, and solubility. Here, we explore the potential of predicting and reducing the aggregation propensity of monoclonal antibodies, based on the identification of aggregation-prone regions and their contribution to the thermodynamic stability of the protein. Although aggregation-prone regions are thought to occur in the antigen binding region to drive hydrophobic binding with antigen, we were able to rationally design variants that display a marked decrease in aggregation propensity while retaining antigen binding through the introduction of artificial aggregation gatekeeper residues. The reduction in aggregation propensity was accompanied by an increase in expression titer, showing that reducing protein aggregation is beneficial throughout the development process. The data presented show that this approach can significantly reduce liabilities in novel therapeutic antibodies and proteins, leading to a more efficient path to clinical studies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Sperm-immobilizing monoclonal antibody to human seminal plasma antigens.

    Science.gov (United States)

    Shigeta, M; Watanabe, T; Maruyama, S; Koyama, K; Isojima, S

    1980-01-01

    Rat spleen cells immunized to human azoospermic semen (a mixture of seminal plasma components) and mouse myeloma cells (P3/X63 Ag8U1; P3U1) (Marguilies et al., 1976) were successfully fused with polyethylene glycol (PEG 1500) and 19 of 89 fused cell cultures were found to produce sperm-immobilizing antibody. The cells that produced antibody indicating the highest sperm-immobilizing activity were distributed into wells for further recloning and 10 clones producing sperm-immobilizing antibody were established. The clone (1C4) producing the highest antibody titre was found to produce a large amount of IgG in culture supernatants and to contain a mixture of rat and mouse chromosomes. It was proved by immunodiffusion test that the monoclonal antibody was produced to the human seminal plasma antigen No. 7 which is common to human milk protein. Using this hybridoma which produced a large amount of monoclonal sperm-immobilizing antibody, a new method could be developed for purifying human seminal plasma antigen by immunoaffinity chromatography with bound antibody from the hybridoma. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6783353

  6. [Obtaining monoclonal antibodies against outer membrane glycoproteins of Entamoeba histolytica].

    Science.gov (United States)

    Agundis, C; Isibasi, A; Ortíz, V; Reyes, J L; Paniagua, J; Ramírez, A; Kumate, J

    1990-01-01

    The goal of this paper was the production of monoclonal antibodies capable of detecting relevant antigens from the surface of Entamoeba histolytica trophozoites, with the purpose of using them as a diagnostic test. The cellular fusion for obtaining the monoclonal antibodies (mAb) was done with spleen cells from BALB/c mice, previously immunized with glycoproteins from the membrane, as well as Sp2/0 cells. The hybridoma supernatants were tested with ELISA, using glycoproteins and lipopeptide phosphoglycans (LPPG) as antigens. Seven hybridomas producing mAb against the glycoproteins were found. Among these, three recognize LPPG. The ability of reacting with the mAb against two molecules disappeared for all the LPPG positive ones when were treated with meta-periodate, and only three reacted against the glycoproteins. All of the mAb were of the Ig M isotypes. They were characterized by Dot blot and Western blot assays. From the results, one may deduce that some mAb recognize as epitopes the polysaccharide portion, and thus infer that they are directed of against the surface and therefore, in the future, could be used with a diagnostic purpose.

  7. Immunotherapy of hepatoma with a monoclonal antibody against murine endoglin

    Institute of Scientific and Technical Information of China (English)

    Guang-Hong Tan; Feng-Ying Huang; Hua Wang; Yong-Hao Huang; Ying-Ying Lin; Yue-Nan Li

    2007-01-01

    AIM: To explore the capability of a monoclonal antibody(mAb) against murine endoglin to inhibit tumor angiogenesis and suppression of hepatoma growth in murine models.METHODS: A monoclonal antibody against murine endoglin was purified by affinity chromatography and passively transfused through tail veins in two murine hepatoma models. Tumor volume and survival time were observed at three-day intervals for 48 d. Microvessels in tumor tissues were detected by immunohistochemistry against CD31, and angiogenesis in vivo was determined by alginate encapsulated assay. In addition, tumor cell apoptosis was detected by TUNEL assay.RESULTS: Passive immunotherapy with anti-endoglin mAb could effectively suppress tumor growth, and prolonged the survival time of hepatoma-bearing mice.Angiogenesis was apparently inhibited within the tumor tissues, and the vascularization of alginate beads was also reduced in the mice passively transfused with antiendoglin mAb. In addition, increased apoptotic cells were observed within the tumor tissues from the mice passively transfused with anti-endoglin mAb.CONCLUSION: Passive immunotherapy with antiendoglin mAb effectively inhibits tumor growth via inhibiting tumor angiogenesis and increasing tumor cell apoptosis, which may be highly correlated with the blockage of endoglin-related signal pathway induced by anti-endoglin mAb.

  8. Generation of monoclonal antibodies against highly conserved antigens.

    Directory of Open Access Journals (Sweden)

    Hongzhe Zhou

    Full Text Available BACKGROUND: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach. METHODOLOGY/PRINCIPAL FINDINGS: In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1 and one mouse self-antigen (TNF-alpha as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system. CONCLUSIONS/SIGNIFICANCE: We developed an efficient and universal method for generating surrogate or therapeutic antibodies against "difficult antigens" to facilitate the development of therapeutic antibodies.

  9. Characterization of oxidative carbonylation on recombinant monoclonal antibodies.

    Science.gov (United States)

    Yang, Yi; Stella, Cinzia; Wang, Weiru; Schöneich, Christian; Gennaro, Lynn

    2014-05-20

    In the biotechnology industry, oxidative carbonylation as a post-translational modification of protein pharmaceuticals has not been studied in detail. Using Quality by Design (QbD) principles, understanding the impact of oxidative carbonylation on product quality of protein pharmaceuticals, particularly from a site-specific perspective, is critical. However, comprehensive identification of carbonylation sites has so far remained a very difficult analytical challenge for the industry. In this paper, we report for the first time the identification of specific carbonylation sites on recombinant monoclonal antibodies with a new analytical approach via derivatization with Girard's Reagent T (GRT) and subsequent peptide mapping with high-resolution mass spectrometry. Enhanced ionization efficiency and high quality MS(2) data resulted from GRT derivatization were observed as key benefits of this approach, which enabled direct identification of carbonylation sites without any fractionation or affinity enrichment steps. A simple data filtering process was also incorporated to significantly reduce false positive assignments. Sensitivity and efficiency of this approach were demonstrated by identification of carbonylation sites on both unstressed and oxidized antibody bulk drug substances. The applicability of this approach was further demonstrated by identification of 14 common carbonylation sites on three highly similar IgG1s. Our approach represents a significant improvement to the existing analytical methodologies and facilitates extended characterization of oxidative carbonylation on recombinant monoclonal antibodies and potentially other protein pharmaceuticals in the biotechnology industry.

  10. Development of Biodegradable Nanocarriers Loaded with a Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Andrew Gdowski

    2015-02-01

    Full Text Available Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid (PLGA nanoparticles using a water/oil/water double emulsion solvent evaporation technique. This method can be used to prepare protective polymeric nanoparticles for transporting functional antibodies to the cytoplasmic compartment of cancer cells. Nanoparticles were formulated and then characterized using a number of physical and biological parameters. The average nanoparticle size ranged from 221 to 252 nm with a low polydispersity index. Encapsulation efficiency of 16%–22% and antibody loading of 0.3%–1.12% were observed. The antibody molecules were released from the nanoparticles in a sustained manner and upon release maintained functionality. Our studies achieved successful formulation of antibody loaded polymeric nanoparticles, thus indicating that a PLGA-based antibody nanoformulation is a promising intracellular delivery vehicle for a large number of new intracellular antibody targets in cancer cells.

  11. Efficient generation of human IgA monoclonal antibodies.

    Science.gov (United States)

    Lorin, Valérie; Mouquet, Hugo

    2015-07-01

    Immunoglobulin A (IgA) is the most abundant antibody isotype produced in humans. IgA antibodies primarily ensure immune protection of mucosal surfaces against invading pathogens, but also circulate and are present in large quantities in blood. IgAs are heterogeneous at a molecular level, with two IgA subtypes and the capacity to form multimers by interacting with the joining (J) chain. Here, we have developed an efficient strategy to rapidly generate human IgA1 and IgA2 monoclonal antibodies in their monomeric and dimeric forms. Recombinant monomeric and dimeric IgA1/IgA2 counterparts of a prototypical IgG1 monoclonal antibody, 10-1074, targeting the HIV-1 envelope protein, were produced in large amounts after expression cloning and transient transfection of 293-F cells. 10-1074 IgAs were FPLC-purified using a novel affinity-based resin engrafted with anti-IgA chimeric Fabs, followed by a monomers/multimers separation using size exclusion-based FPLC. ELISA binding experiments confirmed that the artificial IgA class switching of 10-1074 did not alter its antigen recognition. In summary, our technical approach allows the very efficient production of various forms of purified recombinant human IgA molecules, which are precious tools in dissecting IgA B-cell responses in physiological and pathophysiological conditions, and studying the biology, function and therapeutic potential of IgAs.

  12. Selfies, Healthies, Usies, Felfies

    DEFF Research Database (Denmark)

    Fausing, Bent

    2014-01-01

    Spejlet hører til en af de skelsættende nyopfindelser, der udbredes i renæssancen og sætter selvet og subjektet i centrum. Det samme gør den såkaldte selfie, der siden den for alvor blev populær i løbet af sidste halvdel af 2013 har udmøntet sig i adskillige underkategorier: Healthies, Usies...

  13. Many Healthy Returns

    Centers for Disease Control (CDC) Podcasts

    2010-02-08

    International travel is usually very safe but there are things you should do to stay safe and healthy. Experts show you how to avoid problems when visiting developing nations. This includes being cautious about the food you eat and the water you drink, and to be aware of vehicles and road conditions to prevent problems.  Created: 2/8/2010 by National Center for Emerging and Zoonotic Infectious Disease (NCEZID).   Date Released: 2/8/2010.

  14. Selfies, Healthies, Usies, Felfies

    DEFF Research Database (Denmark)

    Fausing, Bent

    2014-01-01

    Spejlet hører til en af de skelsættende nyopfindelser, der udbredes i renæssancen og sætter selvet og subjektet i centrum. Det samme gør den såkaldte selfie, der siden den for alvor blev populær i løbet af sidste halvdel af 2013 har udmøntet sig i adskillige underkategorier: Healthies, Usies...

  15. Healthy Maternal Ambivalence

    OpenAIRE

    Raphael-Leff, Joan

    2010-01-01

    This paper critically reviews the psychoanalytic omission in theorizing maternal subjectivity and the subsequent idealisation of the early mother-baby bond that excludes negative maternal feelings. It suggests that painful maternal experiences of resentment, persecution and hatred remain under-explored. Perhaps, even more alarming, this exclusion compels mothers to hide conflictual and shameful feelings from professionals – and from themselves. The paper suggests that healthy maternal ambival...

  16. Current status of cancer immunodetection with radiolabeled human monoclonal antibodies.

    Science.gov (United States)

    De Jager, R; Abdel-Nabi, H; Serafini, A; Pecking, A; Klein, J L; Hanna, M G

    1993-04-01

    The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting

  17. Healthy Aging in China.

    Science.gov (United States)

    Smith, James P; Strauss, John; Zhao, Yaohui

    2014-12-01

    China has aged rapidly and the rate is accelerating in decades to come. We review positive and negative forces for healthy aging in China now and in the future. The most positive force is the spectacular growth in education over time especially for Chinese women, which should improve all dimensions of cognitive and physical health and eliminate vast gender disparities in healthy aging that currently exist. Other positive forces include increasing detection and treatment of disease and the availability of health insurance and health services so that diseases like hypertension and diabetes do not remain silent killers in China. Transparency is eased on the research level by publicly available data such as CHARLS, a sharp departure from prior scientific norm in China. Negative forces center on disturbing trends in personal health behaviors such as growing rates of smoking (among men) and obesity (for both genders), and pollution-,especially in urban centers. Public health campaigns and incentives are needed on all these fronts so that predictable long-term consequences of these behaviors on older age disease are not realized. There will not be a simple demographic fix to healthy aging in China as fertility rates are unlikely to rise much, while migration will likely continue to rise leaving growing numbers of elderly parents geographically separated from their adult children. Government policy will have to allow migration of elderly parents to live with their adult children while reducing the rigid connection of policy (health insurance and health services) with place of residence.

  18. A Healthy Person

    Directory of Open Access Journals (Sweden)

    Sevald Høye

    2016-05-01

    Full Text Available The purpose of this exploratory study was to investigate how nursing students in Indonesia and Scandinavia characterize a healthy person. Two hundred thirty-two nursing students from Indonesia, 50 students from Sweden, and 119 students from Norway participated by answering an open-ended question. Qualitative content analysis was used to identify patterns of health in a cultural and national context. The characteristics of a healthy person were summarized in the theme “external and inner balance,” which are intertwined because of the wholeness of self-image and appearance. The subcategories were having a strong and positive body image, feeling well and having inner harmony, following the rules of life, coping with challenges, and acting in unison with the environment. There were more similarities than differences between the Indonesian and Scandinavian nursing students’ understanding of being a healthy person. The difference is that the Scandinavian students mentioned individuality, whereas the Indonesian students referred to collective values.

  19. A Healthy Person

    Directory of Open Access Journals (Sweden)

    Sevald Høye

    2016-05-01

    Full Text Available The purpose of this exploratory study was to investigate how nursing students in Indonesia and Scandinavia characterize a healthy person. Two hundred thirty-two nursing students from Indonesia, 50 students from Sweden, and 119 students from Norway participated by answering an open-ended question. Qualitative content analysis was used to identify patterns of health in a cultural and national context. The characteristics of a healthy person were summarized in the theme “external and inner balance,” which are intertwined because of the wholeness of self-image and appearance. The subcategories were having a strong and positive body image, feeling well and having inner harmony, following the rules of life, coping with challenges, and acting in unison with the environment. There were more similarities than differences between the Indonesian and Scandinavian nursing students’ understanding of being a healthy person. The difference is that the Scandinavian students mentioned individuality, whereas the Indonesian students referred to collective values.

  20. Empowering a healthy practice environment.

    Science.gov (United States)

    Kushner, Jodi; Ruffin, Tasha

    2015-03-01

    This article provides frontline nurses a tool kit so they can advocate a healthy practice environment. The healthy nurse, healthy work hours, job satisfaction, adequate sleep, power naps at work, and balancing family/work are discussed. The overweight nurse, nurse fatigue, compassion fatigue, shift work sleep disorder, and role strain are discussed as barriers to a healthy practice environment. Case reports with analysis and recommendations are discussed to overcome these barriers. Resources are presented for frontline nurses to develop a tool kit for transforming their environment to a healthy practice environment and to empower them to become healthy nurses.

  1. Monoclonal antibodies against a synthetic peptide from human immunodeficiency virus type 1 Nef protein

    DEFF Research Database (Denmark)

    Steinaa, L; Wulff, A M; Saermark, T

    1994-01-01

    Monoclonal antibodies against a synthetic peptide (aa 138-152) from HIV-1 Nef protein were produced and characterized. Three hybridoma lines producing monoclonal antibodies (MAbs) against the synthetic peptide were generated by fusion between P3-X63 Ag8.653 myeloma cells and BALB/c splenocytes fr...

  2. Preparation of Europium Induced Conformation—specific anti—calmodulin Monoclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    WeiGuoLI; ChaoQI; 等

    2002-01-01

    Monoclonal antibody technique was employed to detect the conformational difference of CaM induced by metal ions. A trivalent europium ion induced conformation-specific anti-calmodulin monoclonal antibody was successfully prepared with europium-saturated calmodulin as antigen.

  3. Preparation of Europium Induced Conformation-specific anti-calmodulin Monoclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Monoclonal antibody technique was employed to detect the conformational difference of CaM induced by metal ions. A trivalent europium ion induced conformation-specific anti-calmodulin monoclonal antibody was successfully prepared with europium-saturated calmodulin as antigen.

  4. Development and characterization of mouse monoclonal antibodies specific for chicken interleukin 18

    Science.gov (United States)

    Four mouse monoclonal antibodies (mAbs) which are specific for chicken interleukin 18 (chIL18) were produced and characterized by enzyme-linked immunosorbent assay (ELISA), Western blotting, quantitative real-time PCR and neutralization assays. Monoclonal antibodies specific for chIL18 identified a ...

  5. Use of commercially available rabbit monoclonal antibodies for immunofluorescence double staining

    DEFF Research Database (Denmark)

    Bzorek, M.; Stamp, I.M.; Frederiksen, L.

    2008-01-01

    Immunohistochemistry, that is, the use of polyclonal and monoclonal antibodies to detect cell and tissue antigens at a microscopical level is a powerful tool for both research and diagnostic purposes. Especially in the field of hematologic disease, there is often a need to detect several antigens...... synchronously, and we report here a fast and easy technique for demonstrating more than 1 antigen in 1 slide using immunofluorescence. We have used commercially available rabbit monoclonal antibodies (Cyclin D1, CD3, CD5, CD23, etc.) paired with mouse monoclonal antibodies (CD7, CD20, CD79a, Pax-5, etc.......) for double immunofluorescence labeling on paraffin-embedded tissue sections. Commercially available rabbit monoclonal antibodies in combination with mouse monoclonal antibodies proved useful in double immunofluorescence labeling on paraffin-embedded tissue, and all combinations used yielded excellent results...

  6. Vitamin Supplements: Healthy or Hoax?

    Science.gov (United States)

    ... Recognition & Awards Healthy Workplace Food and Beverage Toolkit Vitamin Supplements: Healthy or Hoax? Updated:Jun 12,2015 Can vitamin and mineral supplements really make you healthier? Overwhelmed ...

  7. Healthy Swimming/Recreational Water

    Science.gov (United States)

    ... Now Available! Q&A with Missy Franklin: Olympic Gold Medalist and Healthy Swimming Champion New Report on ... enter your email address: Enter Email Address Submit Button What's this? Healthy Swimming Swimmers Health Benefits of ...

  8. What Makes a Healthy Pregnancy?

    Science.gov (United States)

    ... of an inherited disorder, such as sickle cell anemia, thalassemia, or Tay-Sachs disease; to screen for common genetic disorders, such as spina bifida and Down syndrome. Read More "Healthy Pregnancy" Articles What Makes a Healthy Pregnancy? / Always Meant ...

  9. Population pharmacokinetic and pharmacodynamic analysis of BIIB023, an anti-TNF-like weak inducer of apoptosis (anti-TWEAK) monoclonal antibody.

    Science.gov (United States)

    Galluppi, Gerald R; Wisniacki, Nicolas; Stebbins, Chris

    2016-07-01

    Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is implicated in the pathogenesis of lupus nephritis. This study evaluated the pharmacokinetics, using the population approach, and pharmacodynamics of BIIB023, an anti-TWEAK monoclonal antibody, in healthy Chinese, Japanese and Caucasian volunteers. In this single-dose, randomized, double-blind, phase 1 study of BIIB023 in healthy volunteers, BIIB023 was administered by intravenous infusion (3 or 20 mg kg(-1) ) on Day 1; follow-up occurred through Day 71. BIIB023 serum concentration was measured using a validated enzyme-linked immunosorbent assay; BIIB023 concentration-time data were subjected to noncompartmental analysis. Population pharmacokinetic analysis was performed using data from this study and a prior phase 1 study of BIIB023 in subjects with rheumatoid arthritis. Soluble TWEAK and BIIB023 complex were evaluated. There were no differences in BIIB023 pharmacokinetics requiring dose adjustment among the three ethnic groups or between healthy volunteers and arthritis patients. BIIB023 central compartment volume (3050 ml) and clearance (7.42 ml h(-1) ) were comparable to those observed for other monoclonal antibody drugs. BIIB023 serum exposure increased in a dose-dependent manner in all groups, but not in direct proportion to dose level; at concentrations below ~10 μg ml(-1) , nonlinear clearance was observed. Soluble TWEAK levels decreased to below the level of quantitation after BIIB023 treatment, with concomitant changes in BIIB023 complex levels. No clinically meaningful differences were observed in BIIB023 pharmacokinetic and pharmacodynamic properties in healthy Chinese, Japanese and Caucasian volunteers; pharmacodynamic measures suggested target engagement. TWEAK may be an attractive therapeutic target for lupus nephritis treatment. © 2016 The British Pharmacological Society.

  10. [Food additives and healthiness].

    Science.gov (United States)

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects.

  11. Healthy eating at schools

    DEFF Research Database (Denmark)

    Sabinsky, Marianne

    . The present PhD thesis is based on evaluation of the dietary effect of this project. There is room for improvement of the dietary habits of Danish children. Dietary habits are influenced by multiple factors across different contexts. The school setting is known as a suitable arena for promotion of healthy...... into account the multiple factors and environments which affect the dietary habits of children. The focus of such an intervention could be implementation of a sustainable school food programme. Another focus could be improvement of the packed lunches brought from home with the purpose to contribute...

  12. Healthy Smile for Your Baby

    Science.gov (United States)

    ... your baby’s gums or brush your baby’s teeth, give your baby healthy foods, and take your baby to the dentist by the time ... they have teeth, you should clean their gums. Give your baby a healthy start! Here are tips ... healthy. Take Care of Your Baby’s Mouth m Clean your ...

  13. Challenges and opportunities for monoclonal antibody therapy in veterinary oncology.

    Science.gov (United States)

    Beirão, Breno C B; Raposo, Teresa; Jain, Saurabh; Hupp, Ted; Argyle, David J

    2016-12-01

    Monoclonal antibodies (mAbs) have come to dominate the biologics market in human cancer therapy. Nevertheless, in veterinary medicine, very few clinical trials have been initiated using this form of therapy. Some of the advantages of mAb therapeutics over conventional drugs are high specificity, precise mode of action and long half-life, which favour infrequent dosing of the antibody. Further advancement in the field of biomedical sciences has led to the production of different forms of antibodies, such as single chain antibody fragment, Fab, bi-specific antibodies and drug conjugates for use in diagnostic and therapeutic purposes. This review describes the potential for mAbs in veterinary oncology in supporting both diagnosis and therapy of cancer. The technical and financial hurdles to facilitate clinical acceptance of mAbs are explored and insights into novel technologies and targets that could support more rapid clinical development are offered. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Effect of polyol sugars on the stabilization of monoclonal antibodies.

    Science.gov (United States)

    Nicoud, Lucrèce; Cohrs, Nicholas; Arosio, Paolo; Norrant, Edith; Morbidelli, Massimo

    2015-02-01

    We investigate the impact of sugars and polyols on the heat-induced aggregation of a model monoclonal antibody whose monomer depletion is rate-limited by protein unfolding. We follow the kinetics of monomer consumption by size exclusion chromatography, and we interpret the results in the frame of two mechanistic schemes describing the enhanced protein stability in the presence of polyols. It is found that the stabilization effect increases with increasing polyol concentration with a comparable trend for all of the tested polyols. However, the stabilization effect at a given polyol concentration is polyol specific. In particular, the stabilization effect increases as a function of polyol size until a plateau is reached above a critical polyol size corresponding to six carbon atoms. Our results show that the stabilization by polyols does not depend solely on the volume fraction filled by the polyol molecules, but is also affected by the polyol chemistry.

  15. Characteristics of Monoclonal Antibody Against Infectious Bursal Disease Virus

    Institute of Scientific and Technical Information of China (English)

    LiYan-Fei; WangWei; 等

    1999-01-01

    Thirteen strains of monoclonal antibodies(McAbs) against infections bursal disease virus(IBDV) were obtained by using hydridoma technique and their characteristics were studied by double immunodiffusion,enzyme-linked immunosorbent assay(ELISA),virus neutralization test(VNT) and Western-blotting assay (WBA).The result showed that nine of the thirteen McAbs belonged to IgG class and four of them belonged to IgM class.No crossreactions were detected betwween the McAbs and Newscastle disease virus (NDV),infectious bronchitis virus(IBV) and Marek's disease virus(MDV).All of McAbs were positively specific reactive with IBDV and five of them can neutralize viral infectivity.Their recognized epitopes of the neutralizing McAbs were all presented on VP2 of the IBDV.

  16. Characteristics of Monoclonal Antibody Against Infectious Bursal Disease Virus

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Thirteen strains of monoclonal antibodies (McAbs) against infectious bursal disease virus (IBDV) were obtained by using hybridoma technique and their characteristics were studied by double immunodiffusion,en- zyme- linked immunosorbent assay (ELISA), virus neutralization test (VNT) and Western- blotting assay (WBA). The result showed that nine of the thirteen McAbs belonged to IgG class and four of them belonged to IgM class. No crossreactions were detected betwween the McAbs and Newscastle disease virus (NDV) ,in- fectious bronchitis virus(IBV) and Marek's disease virus(MDV). All of McAbs were positively specific reac- tive with IBDV and five of them can neutralize viral infectivity. Their recognized epitopes of the neutralizing McAbs were all presented on VP2 of the IBDV.

  17. Preparation and Identification of Monoclonal Antibodies Against Vibrio anguillarum

    Institute of Scientific and Technical Information of China (English)

    Chen Shiyong(陈师勇); Zhang Peijun; Mo Zhaolan; Zhang Zhendong; Zou Yuxia; Xu Yongli

    2004-01-01

    Monoclonal antibodies (Mabs) against V.anguillarum strain M3 are prepared, and their isotypes are also characterized. Among them, C1C5 is the only Mab which does not crossreact with other eleven non-V.anguillarum strains. The proteinase K digestion test shows that the epitopes recognized by C1C5, C6C3 and C6C32 Mabs contained protein. The periodate oxidation test showed that the epitopes recognized by Mabs except C1C5 are glycosylated. In addition, results of additivity test indicate that the epitopes recognized by C6C3 and C6C32 Mabs are similar, and quite different from those recognized by Mab C1C5.

  18. [Monoclonal antibodies for the treatment of multiple sclerosis].

    Science.gov (United States)

    Sánchez-Seco, Victoria Galán; Casanova Peño, Ignacio; Arroyo González, Rafael

    2014-12-01

    Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  19. Pharmacokinetic, pharmacodynamic and immunogenicity comparability assessment strategies for monoclonal antibodies.

    Science.gov (United States)

    Putnam, Wendy S; Prabhu, Saileta; Zheng, Yanan; Subramanyam, Meena; Wang, Yow-Ming C

    2010-10-01

    Regulatory guidance stipulates that comparability assessment is required to support manufacturing process changes during the development of a biological product or post-approval. However, strategies for assessing the comparability of pre- and post-change materials are still evolving. A hierarchical risk-based approach is recommended, starting with analytical testing to ensure quality, followed by biological characterization and, if needed, in vivo pharmacokinetic (PK), PK-pharmacodynamic (PD), safety and/or efficacy studies. The need for an in vivo study and the type of study required depend on the magnitude and the potential impact of the changes and the timing in the development process. This review discusses factors affecting the PK, PD and immunogenicity of monoclonal antibodies, and provides guidance for determining non-clinical and clinical comparability assessment strategies. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Moving through three-dimensional phase diagrams of monoclonal antibodies.

    Science.gov (United States)

    Rakel, Natalie; Baum, Miriam; Hubbuch, Jürgen

    2014-01-01

    Protein phase behavior characterization is a multivariate problem due to the high amount of influencing parameters and the diversity of the proteins. Single influences on the protein are not understood and fundamental knowledge remains to be obtained. For this purpose, a systematic screening method was developed to characterize the influence of fluid phase conditions on the phase behavior of proteins in three-dimensional phase diagrams. This approach was applied to three monoclonal antibodies to investigate influences of pH, protein and salt concentrations, with five different salts being tested. Although differences exist between the antibodies, this extensive study confirmed the general applicability of the Hofmeister series over the broad parameter range analyzed. The influence of the different salts on the aggregation (crystallization and precipitation) probability was described qualitatively using this Hofmeister series, with a differentiation between crystallization and precipitation being impossible, however.

  1. PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia.

    Science.gov (United States)

    Ito, Matthew K; Santos, Raul D

    2017-01-01

    Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid-modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achieve optimal reduction in lipids for some patients, including those who have or are at high risk for cardiovascular disease. The PCSK9 gene was identified in the past decade as a potential therapeutic target for the management of patients with hypercholesterolemia. Pharmacologic interventions to decrease PCSK9 levels are in development, with the most promising approach using monoclonal antibodies that bind to PCSK9 in the plasma. Two monoclonal antibodies, alirocumab and evolocumab, have recently been approved for the treatment of hypercholesterolemia, and a third one, bococizumab, is in phase 3 clinical development. All 3 agents achieve significant reductions in levels of low-density lipoprotein cholesterol, as well as reductions in non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). Long-term outcome trials are under way to determine the sustained efficacy, safety, and tolerability of PCSK9 inhibitors and whether this novel class of agents decreases the risk for major cardiovascular events in patients on lipid-modifying therapy. Available data suggest that PCSK9 inhibitors provide a robust reduction in atherogenic cholesterol levels with a good safety profile, especially for patients who fail to obtain an optimal clinical response to statin therapy, those who are statin intolerant or have contraindications to statin therapy, and those with familial hypercholesterolemia. © 2016, The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  2. Detection of experimental myocarditis by monoclonal antimyosin antibody, Fab fragment

    Energy Technology Data Exchange (ETDEWEB)

    Rezkalla, S.; Kloner, R.A.; Khaw, B.A.; Haber, E.; Fallon, J.T.; Smith, F.E.; Khatib, R.

    1989-02-01

    The purpose of this study was to determine whether monoclonal antimyosin Fab (antigen binding fragment) was capable of labeling hearts with experimental coxsackievirus myocarditis, and to determine whether Fab could be used for detecting myocardial damage in either early or chronic phases of the disease. Sixty-five, 3-week-old cesarean-derived 1 (CD 1) mice were divided into two groups: group I (noninfected animals) and group II (infected with coxsackievirus B3). Mice from each group were killed on days 7, 17, 30, or 90 of infection. Forty-eight hours before killing, mice were injected with monoclonal I-125 antimyosin, Fab (25 microCi/injection) and radioactivity was counted in the heart. Selected heart sections were also examined by autoradiography. Heart radioactivity, count/m/mg (m +/- SEM) on days 7, 17, 30, and 90 of infection was 10.8 +/- 1.7, 21.3 +/- 1.1, 11.2 +/- 3.4, and 12.4 +/- 1.5 for group I, versus 36.7 +/- 8.0 (p less than 0.01), 50.0 +/- 4.5 (p less than 0.001), 33.4 +/- 16.1 (p = NS), and 40.6 +/- 8.5 (p less than 0.01) for group II, respectively. Autoradiography revealed focal uptake within areas of necrotic myocardium. We conclude that I125 Fab may be useful in detecting myocardial damage in the experimental model of murine myocarditis up to day 90 of infection.

  3. A partner monoclonal antibody to Moab 730 kills 100% of DU145 and PC3 androgen-independent cancer cells

    Indian Academy of Sciences (India)

    Hemant Kumar Vyas; Rahul Pal; Nirmal K Lohiya; G P Talwar

    2009-12-01

    A number of therapeutic options are available for patients with prostate carcinoma till the time that the tumour is hormone dependent. However, no fully effective therapy is available for the treatment of androgen-independent prostate carcinomas. Antibodies directed at epitopes unique to or overexpressed on the cancer cells could be of therapeutic utility. A monoclonal antibody (Moab) 2C4 has been generated, which binds with cells of two androgenindependent prostate cancers, DU145 and PC3, and does not bind to peripheral blood leukocytes (PBLs) of healthy donors. This antibody, along with the previously developed Moab 730, kills 100% of both DU145 and PC3 cells in the presence of complement and does not have a deleterious effect on PBLs of healthy males. The anti-tumour action of the two antibodies prevents the establishment of DU145 cell tumour in nude mice in vivo. Moab 2C4 in combination with 730 has potential for use as therapy for androgen-independent cancers.

  4. In-vitro inhibition of IFNγ+ iTreg mediated by monoclonal antibodies against cell surface determinants essential for iTreg function

    Directory of Open Access Journals (Sweden)

    Daniel Volker

    2012-08-01

    Full Text Available Abstract Background IFNγ-producing CD4+CD25+Foxp3+ PBL represent a subtype of iTreg that are associated with good long-term graft outcome in renal transplant recipients and suppress alloresponses in-vitro. To study the mechanism of immunosuppression, we attempted to block cell surface receptors and thereby inhibited the function of this iTreg subset in-vitro using monoclonal antibodies and recombinant proteins. Methods PBL of healthy control individuals were stimulated polyclonally in-vitro in the presence of monoclonal antibodies or recombinant proteins against/of CD178, CD152, CD279, CD28, CD95, and HLA-DR. Induction of IFNγ+ iTreg and proliferation of effector cells was determined using four-color fluorescence flow cytometry. Blockade of iTreg function was analyzed using polyclonally stimulated co-cultures with separated CD4+CD25+CD127-IFNγ+ PBL. Results High monoclonal antibody concentrations inhibited the induction of CD4+CD25+Foxp3+IFNγ+ PBL (anti-CD152, anti-CD279, anti-CD95: p +CD25+CD127-IFNγ+ PBL (anti-CD178, anti-CD152, anti-CD279, anti-CD95: p +CD25+Foxp3+IFNγ+ PBL (rCD152 and rCD95: p +CD25+CD127-IFNγ+ PBL showed lower cell proliferation than co-cultures with CD4+CD25+CD127-IFNγ- PBL (p +CD25+CD127-IFNγ- PBL-containing co-cultures in the presence of monoclonal antibody (anti-CD28, anti-CD152, anti-CD279: p +CD25+CD127-IFNγ+ PBL (with the exception anti-CD28 monoclonal antibody: p +CD25+CD127-IFNγ- PBL but do not efficiently block suppressive iTreg function in co-cultures with CD4+CD25+CD127-IFNγ+ PBL. Conclusions CD178, CD152, CD279, CD28, CD95, and HLA-DR determinants are important for induction and suppressive function of IFNγ+ iTreg.

  5. Towards healthy cities.

    Science.gov (United States)

    Satterthwaite, D

    1996-01-01

    Cities contain many of the world's most unhealthy living environments. They are considered ecologically unsustainable because of high consumption and waste levels, attributed to high population density. However, well planned and managed cities can combine high living standards with remarkably low levels of energy consumption, resource use and wastes. The concentration of people and production creates many more possibilities of collecting and recycling wastes and for walking, bicycling and a high quality public transport. This potential for providing healthy, stimulating and valued places to live and work for all age groups could be achieved with good governance. In any city, this approach means encouragement and support from all levels of government for a great range of investments of capital, expertise and time by individuals, households, communities, voluntary organizations and nongovernmental organizations, as well as private enterprises. Moreover, this means managing competing claims and finding common ground between enterprises, trade unions and residents about what should be done to make the city healthier.

  6. Healthy and productive workers

    DEFF Research Database (Denmark)

    Ammendolia, Carlo; Côté, Pierre; Cancelliere, Carol

    2016-01-01

    and stakeholder experience. This was then systematically operationalized into a program using discussion groups and consensus among experts and stakeholders. RESULTS: The top health problem impacting our workplace partner was mental health. Depression and stress were the first and second highest cause...... of productivity loss respectively. A multi-pronged program with detailed action steps was developed and directed at key stakeholders and health conditions. For mental health, regular sharing focus groups, social networking, monthly personal stories from leadership using webinars and multi-media communications......, expert-led workshops, lunch and learn sessions and manager and employee training were part of a comprehensive program. Comprehensive, specific and multi-pronged strategies were developed and aimed at encouraging healthy behaviours that impact presenteeism such as regular exercise, proper nutrition...

  7. Monoclonal Antibody-Based Enzyme Linked Immunosorbent Assay for the Analysis of Jasmonates in Plants

    Institute of Scientific and Technical Information of China (English)

    Aixing Deng; Weiming Tan; Suping He; Wei Liu; Tiegui Nan; Zhaohu Li; Baomin Wang; Qing X.Li

    2008-01-01

    Methyl jasmonate (MeJA) and its free-acid form,jasmonic acid (JA) are naturally occurring plant growth regulators widely distributed in higher plants.In order to improve the sensitivity for the analysis of MeJA at low levels in small amounts of plant samples,a monoclonal antibody (MAb) (designated as MAb 3E5D7C4B6) against MeJA was derived from a JAbovine serum albumin (BSA) conjugate as an immunogen.The antibody belongs to the IgG1 subclass with a κ type light chain and has a dissociation constant of approximately 6.07 x 10-9 M.MAb3E5D7C4B6 is very specific to MeJA.It was used to develop a direct competitive enzyme-linked immunosorbent assay (dcELISA),conventional and simplified indirect competitive ELISAs (icELISA).JA was derivatized into MeJA for the ELISA analysis.The IC50 value and detection range for MeJA were,respectively,34 and 4-257 ng/mL by the conventional icELISA,21 and 3-226 ng/mL by the simplified icELISA and 5.0 and 0.7-97.0 ng/mL by the dcELISA.The dcELISA was more sensitive than either the conventional or simplified icELISA.The assays were used to measure the content of jasmonates as MeJA in tobacco leaves under drought stress or inoculated with tobacco mosaic virus and tomato leaves inoculated with tomato mosaic virus or Lirioinyza sativae Blanchard as compared with the corresponding healthy leaves.The increased jasmonates content indicated its role in response to the drought stress and pathogens.

  8. Down Syndrome in Adults: Staying Healthy

    Science.gov (United States)

    ... Shortfall Questionnaire Home Prevention and Wellness Staying Healthy Down Syndrome in Adults: Staying Healthy Down Syndrome in Adults: Staying Healthy Family HealthPrevention and WellnessStaying ...

  9. Monoclonal antibodies neutralizing the haemolytic activity of box jellyfish (Chironex fleckeri) tentacle extracts.

    Science.gov (United States)

    Collins, S P; Comis, A; Marshall, M; Hartwick, R F; Howden, M E

    1993-09-01

    1. Three monoclonal antibodies have been produced which neutralize in vitro the haemolytic activity present in tentacle extracts of the box jellyfish (Chironex fleckeri). 2. Two of these monoclonal antibodies bound specifically to a component of relative molecular mass 50,000 in tentacle extract on Western blots. 3. This binding only occurred when the extracts were electrophoresed under non-reducing conditions. 4. The third monoclonal antibody did not display binding to Western blots of tentacle extract under any of our experimental conditions.

  10. Efficacy and safety of AVP-21D9, an anthrax monoclonal antibody, in animal models and humans.

    Science.gov (United States)

    Malkevich, Nina V; Hopkins, Robert J; Bernton, Edward; Meister, Gabriel T; Vela, Eric M; Atiee, George; Johnson, Virginia; Nabors, Gary S; Aimes, Ronald T; Ionin, Boris; Skiadopoulos, Mario H

    2014-07-01

    Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human anthrax monoclonal antibody), is being developed as a therapeutic agent against anthrax toxemia. The efficacy of AVP-21D9 in B. anthracis-infected New Zealand White rabbits and in cynomolgus macaques was evaluated, and its safety and pharmacokinetics were assessed in healthy human volunteers. The estimated mean elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11 days, respectively. In healthy humans, the mean elimination half-life was in the range of 20 to 27 days. Dose proportionality was observed for the maximum serum concentration (Cmax) of AVP-21D9 and the area under the concentration-time curve (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in survival of up to 92% of the rabbits and up to 67% of the macaques. Single infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all doses evaluated, and no serious adverse events were reported. (This study has been registered at ClinicalTrials.gov under registration no. NCT01202695.).

  11. Case for diagnosis. Lichen myxedematosus*

    Science.gov (United States)

    Rebellato, Priscila Regina Orso; Carbonar, Mauren Beatriz Frazon; Tabuti, Nicole Iasmin Magario; Rastelli, Graziela Junges Crescente

    2016-01-01

    Scleromyxedema or lichen myxedematosus is a rare papular mucinosis of chronic and progressive course and unknown etiology. It is commonly associated with monoclonal gammopathy and may show extracutaneous manifestations, affecting the heart, lung, kidney, and nerves. The diagnosis is based on four criteria: generalized papular and sclerodermoid lesions; mucin deposition, fibroblast proliferation, and fibrosis in the histopathology; monoclonal gammopathy; and no thyroid disorders. This article reports the case of a scleromyxedema patient with a recent history of acute myocardial infarction and monoclonal gammopathy. PMID:28099617

  12. Dysregulation of CD47 and the ligands thrombospondin 1 and 2 in multiple myeloma

    DEFF Research Database (Denmark)

    Rendtlew Danielsen, Jannie M; Knudsen, Lene Meldgaard; Dahl, Inger Marie

    2007-01-01

    CD47 and thrombospondin 1 and 2 (TSP1 and TSP2) expression were analysed by real-time reverse transcription polymerase chain reaction in fluorescence-activated cell sorted plasma cells (PCs) from patients at consecutive stages of multiple myeloma (MM) development. 80% of MM patients, but only 39......% of patients with monoclonal gammopathy of undetermined significance (MGUS) expressed CD47; median expression level increased 10-fold with progression from MGUS to MM. Elevated TSP1/TSP2 levels occurred in bone marrow cultures from MM patients compared with healthy donors. CD47 and TSP1/TSP2 may have...

  13. Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

    Science.gov (United States)

    Wilkinson, Trevor C I

    2016-06-15

    The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed.

  14. NCI Requests Targets for Monoclonal Antibody Production and Characterization - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution.

  15. THE MECHANISM OF ANTI-IMPLANTATION EFFECT OF PROGESTERONE MONOCLONAL ANTIBODIES IN MICE

    Institute of Scientific and Technical Information of China (English)

    WANGMin-Yi; HEZhi-Ying; WANGHan-Zheng

    1989-01-01

    The purpose of this study is to investigate the mechanism by which antiprogcsterone monoclonal antibodies block early pregnancy in mice. The mechanism of passive immunization is a complex issue as indicated below:

  16. Immunolocation of antisperm monoclonal antibody 6B10 and corresponding antigen

    Institute of Scientific and Technical Information of China (English)

    高绍荣; 胡国俊; 段崇文; 刘辉; 韩之明; 宋祥芬; 陈大元

    1999-01-01

    An antisperm monoclonal antibody 6B10 was produced by hybridoma technique of the isotype IgG. The monoclonal antibody was purified by means of ammonium sulfate precipitation and protein A-Sepharose Cl-4B affinity chromatography. SDS polyacrylamide gel electrophoresis was used to evaluate the purity of the antibody. Evaluation of the sperm acrosomal status was determined by chlortetracycline (CTC) staining. It was found that monoclonal antibody 6B10 can inhibit the sperm acrosome reaction induced by progesterone. The corresponding antigen recognized by monoclonal antibody 6B10 was located on the plasma membrane of the sperm acrosome by indirect immunofluorescent microscopy and immunoelectronmicroscopy. Sperm protein was extracted by 1% Triton X-100. The molecular weight of the antigen is 50 ku, detected by Western blot. The antigen is a key protein in the sperm acrosome reaction and may be the receptor of progesterone on the sperm acrosome. It may either be developed as a candidate contraceptive vaccine

  17. Purification of a Mycoplasma pneumoniae adhesin by monoclonal antibody affinity chromatography.

    OpenAIRE

    Leith, D K; Baseman, J B

    1984-01-01

    A 165,000-dalton surface protein of Mycoplasma pneumoniae, designated protein P1, appears to be the major attachment ligand of the pathogen. We employed monoclonal antibody affinity chromatography to obtain purified protein P1.

  18. The role of radiolabeled anti-TNFα monoclonal antibodies for diagnostic purposes and therapy evaluation

    NARCIS (Netherlands)

    Glaudemans, A. W.J.M.; Dierckx, R. A.J.O.; Kallenberg, C. G.M.; Anzola Fuentes, K. L.

    2010-01-01

    Radiolabelled cytokines and monoclonal antibodies are an emerging class of radiopharmaceuticals for imaging inflammation. These radiopharmaceuticals bind to their targets with high affinity and specificity and therefore have excellent diagnostic potential for imaging of patients with chronic inflamm

  19. CHARACTERIZATION OF MONOCLONAL ANTIBODIES AGAINST BOTH PIG AND RABBIT ZONA PELLUCIDA

    Institute of Scientific and Technical Information of China (English)

    OURU-QIANG

    1989-01-01

    Three monoclonal antibodies (MAbs) were raised against both pig and rabbit zona pellucida with a dual immunization protocol employing heat soluble pig zona (HSPZ) and heat soluble rabbit zona (HSRZ), Of the 140 wells screencd, 12 wells were positive to

  20. HEALTHY LIVING WITH NUTRACEUTICALS

    Directory of Open Access Journals (Sweden)

    Priyanka Singh

    2011-12-01

    Full Text Available Now a day every person wants to live the healthy life. Synthetic medicines are having some certain drawbacks. So nutraceuticals will definitely play promising and unique way of safer medicines. Nature is one of the most important resources of human foods and medicines. Rapidly increasing knowledge on nutrition, medicine, and plant has fortunately changed the concepts about food, health and, brought in a revolution on them. Nutritional therapy and phototherapy have emerged as new concepts of safer medicine. These systems have quickly and widely spread in recent years. Strong recommendations for consumption of nutraceuticals, natural plant foods, and the use of nutritional therapy and phototherapy have become progressively popular to improve health, and to prevent and treat diseases. Nutraceuticals used in various diseases, Alzheimer’s disease, cardiovascular disease, obesity, cancer, eye cycle, diabetes. The use of the dietary fiber, omega 3 fatty acid, antioxidant, probiotic, for the better human life possible. This review attempts to display and remark on these aspects. It summarizes the progress made on nutraceuticals, utritional therapy, health benefits, regulation and their promising approach. It also covers development stages of nutraceuticals.

  1. Global healthy backpack initiatives.

    Science.gov (United States)

    Jayaratne, Kapila; Jacobs, Karen; Fernando, Dulitha

    2012-01-01

    Schoolbag use by children is a global common concern.. Children carry school books and other amenities in their school bags. Global evidence indicates that daily load carried by school children may have negative health implications. Backpack as a school bag model, is the healthiest way of load carriage for school children. Several initiatives have been launched world over to minimize unhealthy consequences resulting from schoolbags. Based on a situation analysis, Sri Lanka implemented a national healthy schoolbag campaign by joint efforts of Ministries of Health and Education. Actions were contemplated on; strategies for bag weight reduction, introduction of an ergonomically modeled schoolbag and bag behaviour change. New strategies were introduced with awareness campaigns to policy makers, bag manufacturers, parents, teachers and children. Four million schoolchildren benefitted. In 2000, the backpack strategy of "Pack it Light, Wear it Right" was started as a public health initiative in the United States by the American Occupational Therapy Association (AOTA). Over the last eleven years, thousands of occupational therapy practitioners and students participated in educational programs and outreach activities. In 2004, modeled after the success AOTA initiative, the Icelandic Occupational Therapy Association launched a national backpack awareness initiative. This article shares examples of practices that could be implemented in any context to the promote health of children.

  2. Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

    Science.gov (United States)

    Minkoff, Marjorie Sue

    A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the

  3. Adolescents' Perceptions of Healthy Eating and Communication about Healthy Eating

    Science.gov (United States)

    Chan, Kara; Prendergast, Gerard; Gronhoj, Alice; Bech-Larsen, Tino

    2009-01-01

    Purpose: The purpose of this paper is to explore Chinese adolescents' perceptions of healthy eating, their perceptions of various socializing agents shaping their eating habits, and their opinions about various regulatory measures which might be imposed to encourage healthy eating. Design/methodology/approach: Four focus group interview sessions…

  4. Adolescents' Perceptions of Healthy Eating and Communication about Healthy Eating

    Science.gov (United States)

    Chan, Kara; Prendergast, Gerard; Gronhoj, Alice; Bech-Larsen, Tino

    2009-01-01

    Purpose: The purpose of this paper is to explore Chinese adolescents' perceptions of healthy eating, their perceptions of various socializing agents shaping their eating habits, and their opinions about various regulatory measures which might be imposed to encourage healthy eating. Design/methodology/approach: Four focus group interview sessions…

  5. Identification of Haemophilus influenzae type b by a monoclonal antibody coagglutination assay.

    OpenAIRE

    Hamel, J.; Brodeur, B R; Belmaaza, A; Montplaisir, S; Musser, J M; Selander, R K

    1987-01-01

    A coagglutination assay using monoclonal antibody is described for the identification of Haemophilus influenzae type b. An immunoglobulin G2a monoclonal antibody, Hb-2, directed against a serotype-specific outer membrane protein of H. influenzae type b was adsorbed to Staphylococcus aureus Cowan 1 cells. In a dot enzyme immunoassay, Hb-2 reacted with 453 of 455 H. influenzae type b isolates and did not react with H. influenzae of other serotypes, untypeable H. influenzae strains, or other bac...

  6. Preparation and Biological Evaluation of 188Re Labeled Monoclonal Antibody TGLA

    Institute of Scientific and Technical Information of China (English)

    WEN; Kai; ZHANG; Jun-li; CHEN; Bao-jun; CUI; Hai-ping

    2012-01-01

    <正>Monoclonal antibody TGLA is a specific targeting CD20 chimeric antibody. It can kill tumor cells and inhibit tumor cells’ growth effectively, which has been applied to clinical therapy of lymphoma cell B. 188 Re is easy to get, and emits both β and γ rays. 188Re labeled monoclonal antibody TGLA can be used for the study of lymphoma therapy and imaging. This work got the product 188Re-TGLA by direct labeling

  7. Efecto de un anticuerpo monoclonal anti CD20 (Rituximab) en trombocitopenia inmune.

    OpenAIRE

    Untama, José; Médico, Departamento de Hematología, Hospital Nacional Edgardo Rebagliati Martins – EsSalud. Lima.; Del Carpio, Daniel; Médico, Departamento de Hematología, Hospital Nacional Edgardo Rebagliati Martins – EsSalud. Lima.

    2012-01-01

    Objetivo: Describir la respuesta terapéutica con un anticuerpo monoclonal anti CD20 (Rituximab), en pacientes con Trombocitopenia Inmune (PTI). Material y métodos: Estudio retrospectivo, descriptivo y observacional tipo serie de casos. Se revisaron las historias clínicas de pacientes adultos con PTI que recibieron el anticuerpo monoclonal anti CD20 (Rituximab), desde diciembre 2005 hasta diciembre 2010. Se definió respuesta: conteo plaquetario >30 mil, por lo menos duplicar el conteo plaqu...

  8. Characterization and evaluation of monoclonal antibodies developed for typing influenza A and influenza B viruses.

    OpenAIRE

    Walls, H H; Harmon, M W; Slagle, J J; Stocksdale, C; Kendal, A P

    1986-01-01

    Monoclonal antibodies that are broadly reactive with influenza A or influenza B viruses were produced as stable reagents for typing influenza viruses. Monoclonal antibodies to influenza A were specific for either matrix protein or nucleoprotein. The antibodies to influenza B were specific for nucleoprotein or hemagglutinin protein. In an enzyme immunoassay procedure, influenza A antibodies detected H1N1, H2N2, and H3N2 influenza A virus strains collected between 1934 and 1984. Each of the inf...

  9. Inhibition of lipoxygenase activity in lentil protoplasts by monoclonal antibodies introduced into the cells via electroporation

    OpenAIRE

    J. F. G. Vliegenthart; Maccarrone, M.; Veldink, G.A.

    1992-01-01

    The isolation of lentil protoplasts and the transfer of anti-lipoxygenase monoclonal antibodies into plant protoplasts by electroporation is reported. The dependence of the efficiency of monoclonal antibody incorporation on the field strength is shown as well. The transferred immunoglobulins retained their functional and structural integrity and were able to inhibit the intracellular target enzyme, with a linear relationship between inhibition of lipoxygenase activity and amount of incorporat...

  10. New monoclonal antibodies directed against human renin. Powerful tools for the investigation of the renin system.

    OpenAIRE

    Galen, F X; Devaux, C.; Atlas, S; Guyenne, T; Menard, J; Corvol, P; Simon, D.; Cazaubon, C; Richer, P; Badouaille, G

    1984-01-01

    Monoclonal antibodies directed against human renin were obtained by the fusing of myeloma cells with spleen cells from Balb/c or high-responder Biozzi mice injected with pure tumoral or highly purified renal renin. These procedures resulted in the production of seven stable monoclonal antibodies to human renin. Antibodies in the hybridoma culture medium were screened by binding to pure iodinated renin or insolubilized renin in a solid phase assay. The concentration of purified antibodies that...

  11. [ICO-166 monoclonal antibodies against the CD45RA antigen].

    Science.gov (United States)

    Frolova, E A; Baryshnikov, A Iu; Novikov, V V; Syrkin, A B

    1993-07-01

    Monoclonal antibodies (MCA) ICO-166 against CD45RA antigen were generated and characterized. In the indirect IFA, MCA ICO-166 reacted with 54.1 +/- 1.9% lymphocytes of human peripheral blood and 15.2 +/- 2.3% monocytes but not with granulocytes or thrombocytes. The method of double labelling of cells demonstrated that MCA ICO-166 detected all B-lymphocytes, all NK-cells and 31% of mature T-lymphocytes but only 55% of CD8 suppressor cells and only 21% of CDA helper cells carried this antigen on the surface. Experiments were carried out to block binding of FITC-labeled MCA ALB11 against CD45RA antigen with human lymphocytes by pretreatment of cells with different concentrations of MCA ICO-166. Treatment of cells with MCA ALB11 blocked binding of MCA ALB11-FITC by 85% on the average. MCA ICO-166 blocked binding of MCA ALB11-FITC by 66% on the average. When different dilutions of MCA ICO-166 were used, the dose-dependent effect of blocking of MCA ALB11-FITC binding was observed. MCA ICO-166 immunoprecipitated a protein band of molecular weight 220 kDa from lysates of mononuclear cells of the human peripheral blood.

  12. Profiling formulated monoclonal antibodies by (1)H NMR spectroscopy.

    Science.gov (United States)

    Poppe, Leszek; Jordan, John B; Lawson, Ken; Jerums, Matthew; Apostol, Izydor; Schnier, Paul D

    2013-10-15

    Nuclear magnetic resonance (NMR) is arguably the most direct methodology for characterizing the higher-order structure of proteins in solution. Structural characterization of proteins by NMR typically utilizes heteronuclear experiments. However, for formulated monoclonal antibody (mAb) therapeutics, the use of these approaches is not currently tenable due to the requirements of isotope labeling, the large size of the proteins, and the restraints imposed by various formulations. Here, we present a new strategy to characterize formulated mAbs using (1)H NMR. This method, based on the pulsed field gradient stimulated echo (PGSTE) experiment, facilitates the use of (1)H NMR to generate highly resolved spectra of intact mAbs in their formulation buffers. This method of data acquisition, along with postacquisition signal processing, allows the generation of structural and hydrodynamic profiles of antibodies. We demonstrate how variation of the PGSTE pulse sequence parameters allows proton relaxation rates and relative diffusion coefficients to be obtained in a simple fashion. This new methodology can be used as a robust way to compare and characterize mAb therapeutics.

  13. Role of cosolutes in the aggregation kinetics of monoclonal antibodies.

    Science.gov (United States)

    Nicoud, Lucrèce; Sozo, Margaux; Arosio, Paolo; Yates, Andrew; Norrant, Edith; Morbidelli, Massimo

    2014-10-16

    We propose a general strategy based on kinetic analysis to investigate how cosolutes affect the aggregation behavior of therapeutic proteins. We apply this approach to study the impact of NaCl and sorbitol on the aggregation kinetics of two monoclonal antibodies, an IgG1 and an IgG2. By using a combination of size exclusion chromatography and light scattering techniques, we study the impact of the cosolutes on the monomer depletion, as well as on the formation of dimers, trimers, and larger aggregates. We analyze these macroscopic effects in the frame of a kinetic model based on Smoluchowski's population balance equations modified to account for nucleation events. By comparing experimental data with model simulations, we discriminate the effect of cosolutes on the elementary steps which contribute to the global aggregation process. In the case of the IgG1, it is found that NaCl accelerates the kinetics of aggregation by promoting specifically aggregation events, while sorbitol delays the kinetics of aggregation by specifically inhibiting protein unfolding. In the case of the IgG2, whose monomer depletion kinetics is limited by dimer formation, NaCl and sorbitol are found respectively to accelerate and inhibit conformational changes and aggregation events to the same extent.

  14. Kinetics of Monoclonal Antibody Aggregation from Dilute toward Concentrated Conditions.

    Science.gov (United States)

    Nicoud, Lucrèce; Jagielski, Jakub; Pfister, David; Lazzari, Stefano; Massant, Jan; Lattuada, Marco; Morbidelli, Massimo

    2016-04-07

    Gaining understanding on the aggregation behavior of proteins under concentrated conditions is of both fundamental and industrial relevance. Here, we study the aggregation kinetics of a model monoclonal antibody (mAb) under thermal stress over a wide range of protein concentrations in various buffer solutions. We follow experimentally the monomer depletion and the aggregate growth by size exclusion chromatography with inline light scattering. We describe the experimental results in the frame of a kinetic model based on population balance equations, which allows one to discriminate the contributions of the conformational and of the colloidal stabilities to the global aggregation rate. Finally, we propose an expression for the aggregation rate constant, which accounts for solution viscosity, protein-protein interactions, as well as aggregate compactness. All these effects can be quantified by light scattering techniques. It is found that the model describes well the experimental data under dilute conditions. Under concentrated conditions, good model predictions are obtained when the solution pH is far below the isoelectric point (pI) of the mAb. However, peculiar effects arise when the solution pH is increased toward the mAb pI, and possible explanations are discussed.

  15. Analysis of viral clearance unit operations for monoclonal antibodies.

    Science.gov (United States)

    Miesegaes, George; Lute, Scott; Brorson, Kurt

    2010-06-01

    Demonstration of viral clearance is a critical step in assuring the safety of biotechnology products. We generated a viral clearance database that contains product information, unit operation process parameters, and viral clearance data from monoclonal antibody and antibody-related regulatory submissions to FDA. Here we present a broad overview of the database and resulting analyses. We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvoviruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log(10) were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses.

  16. DNA immunization as a technology platform for monoclonal antibody induction.

    Science.gov (United States)

    Liu, Shuying; Wang, Shixia; Lu, Shan

    2016-04-06

    To combat the threat of many emerging infectious diseases, DNA immunization offers a unique and powerful approach to the production of high-quality monoclonal antibodies (mAbs) against various pathogens. Compared with traditional protein-based immunization approaches, DNA immunization is efficient for testing novel immunogen designs, does not require the production or purification of proteins from a pathogen or the use of recombinant protein technology and is effective at generating mAbs against conformation-sensitive targets. Although significant progress in the use of DNA immunization to generate mAbs has been made over the last two decades, the literature does not contain an updated summary of this experience. The current review provides a comprehensive analysis of the literature, including our own work, describing the use of DNA immunization to produce highly functional mAbs, in particular, those against emerging infectious diseases. Critical factors such as immunogen design, delivery approach, immunization schedule, use of immune modulators and the role of final boost immunization are discussed in detail.

  17. Characterization of Endotrypanum Parasites Using Specific Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Ramos Franco Antonia Maria

    1997-01-01

    Full Text Available A large number of Endotrypanum stocks (representing an heterogeneous population of strains have been screened against a panel of monoclonal antibodies (MAbs derived for selected species of Endotrypanum or Leishmania, to see whether this approach could be used to group/differentiate further among these parasites. Using different immunological assay systems, MAbs considered specific for the genus Endotrypanum (E-24, CXXX-3G5-F12 or strain M6159 of E. schaudinni (E-2, CXIV-3C7-F5 reacted variably according to the test used but in the ELISA or immunofluorescence assay both reacted with all the strains tested. Analyses using these MAbs showed antigenic diversity occurring among the Endotrypanum strains, but no qualitative or quantitative reactivity pattern could be consistently related to parasite origin (i.e., host species involved or geographic area of isolation. Western blot analyses of the parasites showed that these MAbs recognized multiple components. Differences existed either in the epitope density or molecular forms associated with the antigenic determinants and therefore allowed the assignment of the strains to specific antigenic groups. Using immunofluorescence or ELISA assay, clone E-24 produced reaction with L. equatorensis (which is a parasite of sloth and rodent, but not with other trypanosomatids examined. Interestingly, the latter parasite and the Endotrypanum strains cross-reacted with a number of MAbs that were produced against members of the L. major-L. tropica complex

  18. Desmoids in familial adenomatous polyposis are monoclonal proliferations.

    Science.gov (United States)

    Middleton, S B; Frayling, I M; Phillips, R K

    2000-02-01

    Desmoids are poorly-understood, locally aggressive, non-metastasizing fibromatoses that occur with disproportionate frequency in patients with familial adenomatous polyposis (FAP). Their nature is controversial with arguments for and against a neoplastic origin. Neoplastic proliferations are by definition monoclonal, whereas reactive processes originate from a polyclonal background. We examined clonality of 25 samples of desmoid tissue from 11 female FAP patients by assessing patterns of X-chromosome inactivation to calculate a clonality ratio. Polymerase chain reaction (PCR) amplification of a polymorphic CAG short tandem repeat (STR) sequence adjacent to a methylation-sensitive restriction enzyme site within the human androgen receptor (HUMARA) gene using fluorescent-labelled primers enabled analysis of PCR products by Applied Biosystems Genescan II software. Twenty-one samples from nine patients were informative for the assay. Samples from all informative cases comprised a median of 66% (range 0-75%) clonal cells but from the six patients with a clonality ratio < or =0.5 comprised a median of 71% (65-75%) clonal cells. FAP-associated desmoid tumours are true neoplasms. This may have implications in the development of improved treatment protocols for patients with these aggressive tumours.

  19. Modulation of desmin intermediate filament assembly by a monoclonal antibody

    Science.gov (United States)

    1988-01-01

    We have used a monoclonal antibody against desmin to examine the assembly of intermediate filaments (IF) from their building blocks, the tetrameric protofilaments. The antibody, designated D76, does not cross react with any other IF proteins (Danto, S.I., and D.A. Fischman. 1984. J. Cell Biol. 98:2179-2191). It binds to a region amino-terminal to cys- 324 of avian desmin that is resistant to chymotrypsin and trypsin digestion, and in the electron microscope appears to bind to the ends of tetrameric protofilaments. In combination, these findings suggest that the epitope of the antibody resides at the amino-terminal end of the alpha-helical rod domain. Preincubation of desmin protofilaments with an excess of D76 antibodies blocks their subsequent assembly into IF. In the presence of sub-stoichiometric amounts of antibodies, IF are assembled from protofilaments but they are morphologically aberrant in that (a) they are capped by IgG molecules at one or both ends; (b) they are unraveled to varying degree, revealing a characteristic right- handed helical arrangement of sub-filamentous strands of different diameters. The antibody binds only to the ends but not along the length of desmin IF. The most straightforward explanation for this is that the epitope resides in a part of the desmin molecule that becomes buried within the core of the filament upon polymerization and is therefore inaccessible to the antibody. PMID:2450097

  20. Monoclonal antibody-based candidate therapeutics against HIV type 1.

    Science.gov (United States)

    Chen, Weizao; Dimitrov, Dimiter S

    2012-05-01

    Treatment of HIV-1 infection has been highly successful with small molecule drugs. However, resistance still develops. In addition, long-term use can lead to toxicity with unpredictable effects on health. Finally, current drugs do not lead to HIV-1 eradication. The presence of the virus leads to chronic inflammation, which can result in increased morbidity and mortality after prolonged periods of infection. Monoclonal antibodies (mAbs) have been highly successful during the past two decades for therapy of many diseases, primarily cancers and immune disorders. They are relatively safe, especially human mAbs that have evolved in humans at high concentrations to fight diseases and long-term use may not lead to toxicities. Several broadly neutralizing mAbs (bnmAbs) against HIV-1 can protect animals but are not effective when used for therapy of an established infection. We have hypothesized that HIV-1 has evolved strategies to effectively escape neutralization by full-size antibodies in natural infections but not by smaller antibody fragments. Therefore, a promising direction of research is to discover and exploit antibody fragments as potential candidate therapeutics against HIV-1. Here we review several bnmAbs and engineered antibody domains (eAds), their in vitro and in vivo antiviral efficacy, mechanisms used by HIV-1 to escape them, and strategies that could be effective to develop more powerful mAb-based HIV-1 therapeutics.

  1. Development and Evaluation of Monoclonal Antibodies for Paxilline

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    Chris M. Maragos

    2015-09-01

    Full Text Available Paxilline (PAX is a tremorgenic mycotoxin that has been found in perennial ryegrass infected with Acremonium lolii. To facilitate screening for this toxin, four murine monoclonal antibodies (mAbs were developed. In competitive indirect enzyme-linked immunosorbent assays (CI-ELISAs the concentrations of PAX required to inhibit signal development by 50% (IC50s ranged from 1.2 to 2.5 ng/mL. One mAb (2-9 was applied to the detection of PAX in maize silage. The assay was sensitive to the effects of solvents, with 5% acetonitrile or 20% methanol causing a two-fold or greater increase in IC50. For analysis of silage samples, extracts were cleaned up by adsorbing potential matrix interferences onto a solid phase extraction column. The non-retained extract was then diluted with buffer to reduce solvent content prior to assay. Using this method, the limit of detection for PAX in dried silage was 15 µg/kg and the limit of quantification was 90 µg/kg. Recovery from samples spiked over the range of 100 to 1000 µg/kg averaged 106% ± 18%. The assay was applied to 86 maize silage samples, with many having detectable, but none having quantifiable, levels of PAX. The results suggest the CI-ELISA can be applied as a sensitive technique for the screening of PAX in maize silage.

  2. Monoclonal antibody probe for assessing beer foam stabilizing proteins.

    Science.gov (United States)

    Onishi, A; Proudlove, M O; Dickie, K; Mills, E N; Kauffman, J A; Morgan, M R

    1999-08-01

    A monoclonal antibody (Mab; IFRN 1625) has been produced, which is specific for the most hydrophobic polypeptides responsible for foam stabilization. The binding characteristics of the Mab suggest that it is the conformation of certain hydrophobic polypeptides which is important for foam stabilization. An enzyme-linked immunosorbent assay (ELISA) for assessing the foam-positive form of the foam-stabilizing polypeptides in beer was developed using IFRN 1625. A good correlation was obtained between ELISA determination of foam-stabilizing polypeptides and an empirical means of determining foaming, that is, the Rudin head retention values, for a collection of beers of various foam qualities. Application of the ELISA to different stages of the brewing process showed that the amounts of foam-positive polypeptides increased during barley germination. During the brewing process the proportion of foam-positive polypeptides present after fermentation increased slightly, although a large amount was lost along with other beer proteins during subsequent steps, such as filtering. The present study demonstrates that the amounts of beer polypeptide present in a foam-positive form have a direct relationship with the foaming potential of beer, that their levels are altered by processing, and that there is potential for greater quality control.

  3. Monoclonal antibodies against NS1 protein of Goose parvovirus.

    Science.gov (United States)

    Qiu, Zheng; Tian, Wei; Yu, Tianfei; Li, Li; Ma, Bo; Wang, Junwei

    2012-04-01

    In the present study, monoclonal antibodies (MAbs) against NS1 protein of Goose parvovirus (GPV) were generated. The secreted MAbs were obtained by fusing mouse myeloma cells and spleen cells of BALB/c mice, which were immunized with the plasmid pcDNA3.1-GPV-NS1 and recombinant protein of GPV-NS1. With indirect ELISA, six hybridoma cell lines against GPV-NS1 were screened. The subtypes of the two MAbs were IgG2a; the others were IgM. The light chain was κ. Western blot analysis showed that six MAbs reacted with recombinant protein GPV-NS1. GPV-NS1 was dissected into 15 overlapping epitopes, which were used to react with MAbs in Western blot. Results showed that six MAbs recognized NS1 protein linear B-cell epitopes located at the C-terminus 453-514 aa, 485-542 aa, and 533-598 aa.

  4. Immunomodulatory Monoclonal Antibodies in Combined Immunotherapy Trials for Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Mariana Aris

    2017-08-01

    Full Text Available In the last few years, there has been a twist in cancer treatment toward immunotherapy thanks to the impressive results seen in advanced patients from several tumor pathologies. Cutaneous melanoma is a highly mutated and immunogenic tumor that has been a test field for the development of immunotherapy. However, there is still a way on the road to achieving complete and long-lasting responses in most patients. It is desirable that immunotherapeutic strategies induce diverse immune reactivity specific to tumor antigens, including the so-called neoantigens, as well as the blockade of immunosuppressive mechanisms. In this review, we will go through the role of promising monoclonal antibodies in cancer immunotherapy with immunomodulatory function, especially blocking of the inhibitory immune checkpoints CTLA-4 and PD-1, in combination with different immunotherapeutic strategies such as vaccines. We will discuss the rational basis for these combinatorial approaches as well as different schemes currently under study for cutaneous melanoma in the clinical trials arena. In this way, the combination of “push and release” immunomodulatory therapies can contribute to achieving a more robust and durable antitumor immune response in patients.

  5. Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab.

    Science.gov (United States)

    Brand, Toni M; Iida, Mari; Wheeler, Deric L

    2011-05-01

    The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase belonging to the HER family of receptor tyrosine kinases. Receptor activation upon ligand binding leads to down stream activation of the PI3K/AKT, RAS/RAF/MEK/ERK and PLCγ/PKC pathways that influence cell proliferation, survival and the metastatic potential of tumor cells. Increased activation by gene amplification, protein overexpression or mutations of the EGFR has been identified as an etiological factor in a number of human epithelial cancers (e.g., NSCLC, CRC, glioblastoma and breast cancer). Therefore, targeting the EGFR has been intensely pursued as a cancer treatment strategy over the last two decades. To date, five EGFR inhibitors, including three small molecule tyrosine kinase inhibitors (TKIs) and two monoclonal antibodies have gained FDA approval for use in oncology. Both approaches to targeting the EGFR have shown clinical promise and the anti-EGFR antibody cetuximab is used to treat HNSCC and CRC. Despite clinical gains arising from use of cetuximab, both intrinsic resistance and the development of acquired resistance are now well recognized. In this review we focus on the biology of the EGFR, the role of EGFR in human cancer, the development of antibody-based anti-EGFR therapies and a summary of their clinical successes. Further, we provide an in depth discussion of described molecular mechanisms of resistance to cetuximab and potential strategies to circumvent this resistance.

  6. Monoclonal antibodies: pharmacokinetics as a basis for new dosage regimens?

    Science.gov (United States)

    Azanza, J-R; Sádaba, B; Gómez-Guiu, A

    2015-10-01

    Complete monoclonal IgG antibodies which are in use in clinical practice share some pharmacological properties resulting in high concentrations in plasma. This fact is reflected in their low volumes of distribution, which can also be correlated with a high molecular weight and water solubility. This feature allows a novel approach to be applied to the dosing schedule for this group of drugs with fixed doses being used instead of the initially developed weight- or body surface-adjusted dosing schedules. In addition, the development of a new formulation containing hyaluronidase allows a subcutaneous route of administration to be used, because hyaluronidase creates a space in the subcutaneous tissue that helps antibody absorption. This method requires higher doses, but has allowed testing the feasibility of administering a fixed dose, with no individual dose adjustments based on weight or body surface. Moreover, loading doses are not needed, because the first dose results, within 3 weeks, in minimum concentrations that are higher than effective concentrations.

  7. An update on newer monoclonal antibodies in lymphoma therapy

    Directory of Open Access Journals (Sweden)

    Subhashini Archana Kadavakolan

    2016-01-01

    Full Text Available In 2014, an estimated 9.4% of all new cancers in the US were accounted to hematological cancers. Most of these cancers have a B-cell origin and on the cell surface express antigen CD20-known to restrict B-cells. Considering the intrinsic immune status of the patients receiving chemotherapy, monoclonal antibodies (mAbs are designed to provide active or passive immunotherapy. Clinical success of rituximab-anti-CD20 mAb in the treatment of lymphoma has led to the development of newer generations of mAb to increase the anti-tumor activity. Hence, recent advances in lymphoma therapy are being built on the conventional prototype of anti-CD20 mAb-rituximab. Our review is an update on the advances in lymphoma therapy using mAb against CD20 including the second generation-ofatumumab, veltuzumab, ocrelizumab, and the third-generation mAbs-ocaratuzumab and obinutuzumab.

  8. Plasmid copy number noise in monoclonal populations of bacteria

    Science.gov (United States)

    Wong Ng, Jérôme; Chatenay, Didier; Robert, Jérôme; Poirier, Michael Guy

    2010-01-01

    Plasmids are extra chromosomal DNA that can confer to their hosts’ supplementary characteristics such as antibiotic resistance. Plasmids code for their copy number through their own replication frequency. Even though the biochemical networks underlying the plasmid copy number (PCN) regulation processes have been studied and modeled, no measurement of the heterogeneity in PCN within a whole population has been done. We have developed a fluorescent-based measurement system, which enables determination of the mean and noise in PCN within a monoclonal population of bacteria. Two different fluorescent protein reporters were inserted: one on the chromosome and the other on the plasmid. The fluorescence of these bacteria was measured with a microfluidic flow cytometry device. We show that our measurements are consistent with known plasmid characteristics. We find that the partitioning system lowers the PCN mean and standard deviation. Finally, bacterial populations were allowed to grow without selective pressure. In this case, we were able to determine the plasmid loss rate and growth inhibition effect.

  9. Establishment of a novel monoclonal antibody against LGR5.

    Science.gov (United States)

    Sasaki, Yuka; Kosaka, Hiromichi; Usami, Katsuaki; Toki, Hiroe; Kawai, Hironori; Shiraishi, Norihiko; Ota, Toshio; Nakamura, Kazuyasu; Furuya, Akiko; Satoh, Mitsuo; Hasegawa, Kazumasa; Masuda, Kazuhiro

    2010-04-09

    LGR5 is an orphan G-protein-coupled receptor (GPCR) that is expressed on the cell surface membrane. LGR5 is reported to be overexpressed in colon, liver, and ovary tumor compared to normal tissue. However, a specific ligand for LGR5 has not yet been determined, and the function is still not clear. An LGR5-specific monoclonal antibody (mAb) is needed as a tool for detection and analysis of LGR5 biological function and cancer therapy. To date, no mAb against LGR5 that retains high affinity and specificity has been reported. Here, we report successful establishment and characterization of a mAb (KM4056) that specifically recognizes the extracellular N-terminal domain of human LGR5, but not LGR4 or LGR6. This mAb has potent complement-dependent cytotoxicity (CDC) activity in vitro and shows strong anti-tumor activity in vivo against xenograft model by transplanting LGR5 expressing CHO transfectants into SCID mice. Thus, KM4056 can be a useful tool for detection of LGR5 positive cells and analysis of LGR5 biological function.

  10. ANTITUMOR EFFECTS OF MONOCLONAL ANTIBODY FAB′ FRAGMENT CONTAINING IMMUNOCONJUGATES

    Institute of Scientific and Technical Information of China (English)

    刘小云; 甄永苏

    2002-01-01

    Objective.Using monoclonal antibody (mAb) Fab′ fragment to develop mAb immunoconjugates for cancer. Methods.Fab′ fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DTT),while Fab′ fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by β mercaptoethanol.The conjugation between Fab′ fragment and pingyangmycin (PYM),an antitumor antibiotic,was mediated by dextran T 40.Immunoreactivity of Fab′ PYM conjugates with cancer cells was determined by ELISA,and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay.Antitumor effects of the Fab′ PYM conjugates were evaluated by subcutaneously transplanted tumors in mice. Results.The molecular weight of Fab′ fragment was approximately 53 kD,while the average molecular weight of Fab′ PYM conjugate was 170 kD.The Fab′ PYM conjugates showed immunoreactivity with antigen relevant cancer cells and selective cytotoxicity against target cells.Administered intravenously,Fab′ PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb. Conclusion.Fab′ PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth,suggesting its therapeutic potential in cancer treatment.

  11. [Production and characteristics of monoclonal antibodies to the diphtheria toxin].

    Science.gov (United States)

    Valiakina, T I; Lakhtina, O E; Komaleva, R L; Simonova, M A; Samokhvalova, L V; Shoshina, N S; Kalinina, N A; Rubina, A Iu; Filippova, M A; Vertiev, Iu V; Grishin, E V

    2009-01-01

    Monoclonal antibodies to the diphtheria toxin were produced without cross reactivity with the thermolabile toxin (LT) from Escherichia coli; ricin; choleraic toxin; the SeA, SeB, SeE, SeI, and SeG toxins of staphylococcus; the lethal factor of the anthrax toxin; and the protective antigen of the anthrax toxin. A pair of antibodies for the quantitative determination of the diphtheria toxin in the sandwich variation of enzyme-linked immunosorbent assay (ELISA) was chosen. The determination limit of the toxin was 0.7 ng/ml in plate and 1.6 ng/ml in microchip ELISA. The presence of a secretion from the nasopharynx lavage did not decrease the sensitivity of the toxin determination by sandwich ELISA. The immunization of mice with the diphtheria toxin and with a conjugate of the diphtheria toxin with polystyrene microspheres demonstrated that the conjugate immunization resulted in the formation of hybridoma clones which produced antibodies only to the epitopes of the A fragment of the diphtheria toxin. The immunization with the native toxin caused the production of hybridoma clones which predominantly produced antibodies to the epitopes of the B fragment.

  12. [Monoclonal antibodies against PCSK9: from bench to clinic].

    Science.gov (United States)

    Guijarro Herraiz, Carlos

    2016-05-01

    Antibodies are glycoproteins with high specificity binding to multiple antigens due to the large number of structural conformations of the variable chains. Hybridoma technology (fusion of myeloma cells with immunoglobulin-producing lymphocytes) has allowed the synthesis of large quantities of unique antibodies (monoclonal [mAb]). mAbs were initially murine. Subsequently, chimeric mAbs were developed, followed by humanized mAbs and finally human mAbs. The high selectivity and good tolerance of human mAbs allows their therapeutic administration to block specific exogenous or endogenous molecules. Selective human mAbs to the catalytic domain of PCSK9 have recently been developed. These antibodies block PCSK9, favour low-density lipoprotein receptor recycling and markedly reduce circulating cholesterol. Preliminary studies indicate that lowering cholesterol through anti-PCSK9 antibodies may significantly reduce the cardiovascular complications of arteriosclerosis. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Arteriosclerosis. All rights reserved.

  13. Production and Characterization of Monoclonal Antibody Against Recombinant Human Erythropoietin

    Institute of Scientific and Technical Information of China (English)

    JIE-BO MI; JIN YAN; XIAO-JIE DING; ZHEN-QUAN GUO; MEI-PING ZHAO; WEN-BAO CHANG

    2007-01-01

    Objective To produce specific monoclonal antibody(mAb)against recombinant human erythropoietin(rHuEPO)for development of higmy efficient methods for erythropoietin detection in biological fluids.Methods rHuEPO was covalently coupled with bovine serum albumin(BSA)and the conjugate was used to immunize mice to produce specific mAb against rHuEPO based on hybridoma technology.The obtained F3-mAb was characterized by enzyme-linked immunosorbent assay (ELISA),SDS-PAGE and Western blot.Results The isotype of F3-mAb Was found to be IgM with an affinity constant of 2.1x108 L/mol.The competitive ELISA using the obtained IgM showed a broader linear range and lower detection limit compared with previous work.Conclusions The modification of rHuEPO was proved to be successful in generating required specific mAb with high avidity to rHuEPO.

  14. Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges

    Directory of Open Access Journals (Sweden)

    Caleb D. Marceau

    2014-01-01

    Full Text Available Filoviruses are the causative agents of lethal hemorrhagic fever in human and non-human primates (NHP. The family of Filoviridae is composed of three genera, Ebolavirus, Marburgvirus and Cuevavirus. There are currently no approved vaccines or antiviral therapeutics for the treatment of filovirus infections in humans. Passive transfer of neutralizing antibodies targeting the Ebola virus (EBOV glycoprotein (GP has proven effective in protecting mice, guinea pigs and NHP from lethal challenges with EBOV. In this study, we generated two neutralizing monoclonal antibodies (MAbs, termed S9 and M4 that recognize the GP of EBOV or multiple strains of Marburg virus (MARV, respectively. We characterized the putative binding site of S9 as a linear epitope on the glycan cap of the GP1 subunit of the EBOV-GP. The M4 antibody recognizes an unknown conformational epitope on MARV-GP. Additionally, we demonstrated the post-exposure protection potential of these antibodies in both the mouse and guinea pig models of filovirus infection. These data indicate that MAbs S9 and M4 would be good candidates for inclusion in an antibody cocktail for the treatment of filovirus infections.

  15. Anti-bacterial monoclonal antibodies: back to the future?

    Science.gov (United States)

    Oleksiewicz, Martin B; Nagy, Gábor; Nagy, Eszter

    2012-10-15

    Today's medicine has to deal with the emergence of multi-drug resistant bacteria, and is beginning to be confronted with pan-resistant microbes. This worsening inadequacy of the antibiotics concept, which has ruled infectious medicine in the last six decades creates an increasing unmet medical need that can be addressed by passive immunization. While past experience from the pre-antibiotic era with serum therapy was in many cases encouraging, antibacterial monoclonal antibodies have so far suffered high attrition rates in the clinic, generally from lack of efficacy. Yet, we believe that recent developments in a number of areas such as infectious disease pathogenesis research, translational medicine, mAb engineering, mAb manufacturing and rapid bedside diagnostics are converging to make the medium-term future permissive for antibacterial mAb development. Here, we review antibacterial mAb-based approaches that are or were in clinical development, and may potentially act as paradigms with regards to molecular targets, antibody formats and mode-of-action, pre-clinical validation and selection of most relevant patient populations, in order to increase the likelihood of successful product development in this field.

  16. Defining process design space for monoclonal antibody cell culture.

    Science.gov (United States)

    Abu-Absi, Susan Fugett; Yang, LiYing; Thompson, Patrick; Jiang, Canping; Kandula, Sunitha; Schilling, Bernhard; Shukla, Abhinav A

    2010-08-15

    The concept of design space has been taking root as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. During mapping of the process design space, the multidimensional combination of operational variables is studied to quantify the impact on process performance in terms of productivity and product quality. An efficient methodology to map the design space for a monoclonal antibody cell culture process is described. A failure modes and effects analysis (FMEA) was used as the basis for the process characterization exercise. This was followed by an integrated study of the inoculum stage of the process which includes progressive shake flask and seed bioreactor steps. The operating conditions for the seed bioreactor were studied in an integrated fashion with the production bioreactor using a two stage design of experiments (DOE) methodology to enable optimization of operating conditions. A two level Resolution IV design was followed by a central composite design (CCD). These experiments enabled identification of the edge of failure and classification of the operational parameters as non-key, key or critical. In addition, the models generated from the data provide further insight into balancing productivity of the cell culture process with product quality considerations. Finally, process and product-related impurity clearance was evaluated by studies linking the upstream process with downstream purification. Production bioreactor parameters that directly influence antibody charge variants and glycosylation in CHO systems were identified.

  17. Super-genotype: global monoclonality defies the odds of nature.

    Directory of Open Access Journals (Sweden)

    Johannes J Le Roux

    Full Text Available The ability to respond to natural selection under novel conditions is critical for the establishment and persistence of introduced alien species and their ability to become invasive. Here we correlated neutral and quantitative genetic diversity of the weed Pennisetum setaceum Forsk. Chiov. (Poaceae with differing global (North American and African patterns of invasiveness and compared this diversity to native range populations. Numerous molecular markers indicate complete monoclonality within and among all of these areas (F(ST = 0.0 and is supported by extreme low quantitative trait variance (Q(ST = 0.00065-0.00952. The results support the general-purpose-genotype hypothesis that can tolerate all environmental variation. However, a single global genotype and widespread invasiveness under numerous environmental conditions suggests a super-genotype. The super-genotype described here likely evolved high levels of plasticity in response to fluctuating environmental conditions during the Early to Mid Holocene. During the Late Holocene, when environmental conditions were predominantly constant but extremely inclement, strong selection resulted in only a few surviving genotypes.

  18. Super-genotype: global monoclonality defies the odds of nature.

    Science.gov (United States)

    Le Roux, Johannes J; Wieczorek, Ania M; Wright, Mark G; Tran, Carol T

    2007-07-04

    The ability to respond to natural selection under novel conditions is critical for the establishment and persistence of introduced alien species and their ability to become invasive. Here we correlated neutral and quantitative genetic diversity of the weed Pennisetum setaceum Forsk. Chiov. (Poaceae) with differing global (North American and African) patterns of invasiveness and compared this diversity to native range populations. Numerous molecular markers indicate complete monoclonality within and among all of these areas (F(ST) = 0.0) and is supported by extreme low quantitative trait variance (Q(ST) = 0.00065-0.00952). The results support the general-purpose-genotype hypothesis that can tolerate all environmental variation. However, a single global genotype and widespread invasiveness under numerous environmental conditions suggests a super-genotype. The super-genotype described here likely evolved high levels of plasticity in response to fluctuating environmental conditions during the Early to Mid Holocene. During the Late Holocene, when environmental conditions were predominantly constant but extremely inclement, strong selection resulted in only a few surviving genotypes.

  19. Downstream processing of monoclonal antibodies--application of platform approaches.

    Science.gov (United States)

    Shukla, Abhinav A; Hubbard, Brian; Tressel, Tim; Guhan, Sam; Low, Duncan

    2007-03-15

    This paper presents an overview of large-scale downstream processing of monoclonal antibodies and Fc fusion proteins (mAbs). This therapeutic modality has become increasingly important with the recent approval of several drugs from this product class for a range of critical illnesses. Taking advantage of the biochemical similarities in this product class, several templated purification schemes have emerged in the literature. In our experience, significant biochemical differences and the variety of challenges to downstream purification make the use of a completely generic downstream process impractical. Here, we describe the key elements of a flexible, generic downstream process platform for mAbs that we have adopted at Amgen. This platform consists of a well-defined sequence of unit operations with most operating parameters being pre-defined and a small subset of parameters requiring development effort. The platform hinges on the successful use of Protein A chromatography as a highly selective capture step for the process. Key elements of each type of unit operation are discussed along with data from 14 mAbs that have undergone process development. Aspects that can be readily templated as well as those that require focused development effort are identified for each unit operation. A brief description of process characterization and validation activities for these molecules is also provided. Finally, future directions in mAb processing are summarized.

  20. Pharmacokinetics of biotech drugs: peptides, proteins and monoclonal antibodies.

    Science.gov (United States)

    Lin, Jiunn H

    2009-09-01

    With the advances in recombinant DNA biotechnology, molecular biology and immunology, the number of biotech drugs, including peptides, proteins and monoclonal antibodies, available for clinical use has dramatically increased in recent years. Although pharmacokinetic principles are equally applicable to the large molecule drugs and conventional small molecule drugs, the underlying mechanisms for the processes of absorption, distribution, metabolism and excretion (ADME) of large molecule drugs are often very different from that of small molecule drugs. Therefore, a good understanding of the ADME processes of large molecule drugs is essential in support of the development of therapeutic biologics. The purpose of this article is to review the current knowledge of the ADME processes that govern the pharmacokinetics of biotech drugs. The challenges encountered by orally administered peptide and protein drugs, and the nature of lymphatic absorption after subcutaneous administration will be discussed. In addition, molecular mechanisms of biodistribution, metabolism and renal excretion of biotech drugs will also be discussed. Finally, approaches used for prediction of human pharmacokinetics of protein drugs will be briefly discussed.

  1. Preparation of monoclonal antibody to P53 and its clinical application

    Institute of Scientific and Technical Information of China (English)

    Wenqing Wei; Junhua Wu; Jing Liu; Yuxia Wang

    2013-01-01

    Objective:The aim of this study was to prepare monoclonal antibody against P53, a kind of tumor suppressor protein,and use the antibody initial y in clinical immunoassay. Methods:Monoclonal antibody was prepared and identified via the classic protocol of monoclonal antibody preparation. Identified monoclonal antibodies were purified by af inity chro-matography. Antibody titer was determined by enzyme linked immunosorbent assay (ELISA). The specific binding activity of antibody was detected by Western blotting and immunohistochemistry. Results:Three strains of monoclonal antibodies named 1P15, 2P37 and 3P40 were obtained and purified by af inity chromatography. The purity of antibodies was higher than 90%. The titers of antibodies were more than 1:6000. Western blot and immunohistochemistry assay showed that the specific antibody can combine with endogenous P53 protein in the tumor celllines and determine the expression of P53 in tumor tis-sue. Conclusion:Three strains of monoclonal antibodies with high af inity to P53 were successful y established, which can be used for detecting the expression of P53 in tumor cells or tissue.

  2. Statistical analysis of data from limiting dilution cloning to assess monoclonality in generating manufacturing cell lines.

    Science.gov (United States)

    Quiroz, Jorge; Tsao, Yung-Shyeng

    2016-07-08

    Assurance of monoclonality of recombinant cell lines is a critical issue to gain regulatory approval in biological license application (BLA). Some of the requirements of regulatory agencies are the use of proper documentations and appropriate statistical analysis to demonstrate monoclonality. In some cases, one round may be sufficient to demonstrate monoclonality. In this article, we propose the use of confidence intervals for assessing monoclonality for limiting dilution cloning in the generation of recombinant manufacturing cell lines based on a single round. The use of confidence intervals instead of point estimates allow practitioners to account for the uncertainty present in the data when assessing whether an estimated level of monoclonality is consistent with regulatory requirements. In other cases, one round may not be sufficient and two consecutive rounds are required to assess monoclonality. When two consecutive subclonings are required, we improved the present methodology by reducing the infinite series proposed by Coller and Coller (Hybridoma 1983;2:91-96) to a simpler series. The proposed simpler series provides more accurate and reliable results. It also reduces the level of computation and can be easily implemented in any spreadsheet program like Microsoft Excel. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1061-1068, 2016.

  3. Novel method for the high-throughput production of phosphorylation site-specific monoclonal antibodies

    Science.gov (United States)

    Kurosawa, Nobuyuki; Wakata, Yuka; Inobe, Tomonao; Kitamura, Haruki; Yoshioka, Megumi; Matsuzawa, Shun; Kishi, Yoshihiro; Isobe, Masaharu

    2016-01-01

    Threonine phosphorylation accounts for 10% of all phosphorylation sites compared with 0.05% for tyrosine and 90% for serine. Although monoclonal antibody generation for phospho-serine and -tyrosine proteins is progressing, there has been limited success regarding the production of monoclonal antibodies against phospho-threonine proteins. We developed a novel strategy for generating phosphorylation site-specific monoclonal antibodies by cloning immunoglobulin genes from single plasma cells that were fixed, intracellularly stained with fluorescently labeled peptides and sorted without causing RNA degradation. Our high-throughput fluorescence activated cell sorting-based strategy, which targets abundant intracellular immunoglobulin as a tag for fluorescently labeled antigens, greatly increases the sensitivity and specificity of antigen-specific plasma cell isolation, enabling the high-efficiency production of monoclonal antibodies with desired antigen specificity. This approach yielded yet-undescribed guinea pig monoclonal antibodies against threonine 18-phosphorylated p53 and threonine 68-phosphorylated CHK2 with high affinity and specificity. Our method has the potential to allow the generation of monoclonal antibodies against a variety of phosphorylated proteins. PMID:27125496

  4. Oral endotoxin in healthy adults

    NARCIS (Netherlands)

    vanSaene, JJM; vanSaene, HKF; Martin, MV; Leenstra, T.

    1996-01-01

    This article presents a study that measured oral endotoxin levels in healthy persons with the Limulus amoebocyte lysate microassay. Only young nonsmoking adults with a healthy dentition measured with the plaque index and a good level of oral hygiene based on a twice-daily (morning and evening)

  5. Prepare Healthy Foods with Toddlers

    Science.gov (United States)

    Izumi-Taylor, Satomi; Rike, Cheryl

    2011-01-01

    Toddlers--from about 16 to 36 months--can learn a variety of skills as they prepare food and follow recipes in developmentally appropriate ways. Early childhood teachers are encouraged to support young children's healthy eating habits by offering simple food preparation experiences. When toddlers--and preschoolers--safely prepare healthy snacks,…

  6. Healthy Eating and Academic Achievement

    Centers for Disease Control (CDC) Podcasts

    2014-12-09

    This podcast highlights the evidence that supports the link between healthy eating and improved academic achievement. It also identifies a few actions to support a healthy school nutrition environment to improve academic achievement.  Created: 12/9/2014 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 12/9/2014.

  7. Healthy Border 2020 Embassy Launch

    Science.gov (United States)

    The U.S.-Mexico Border Health Commission launched the Healthy Border 2020 at the Mexican Embassy in the United States on June 24, 2015. This new initiative aims to strengthening what was accomplished on the previous plan of action entitled Healthy Border 2010.

  8. Comparative optimism about healthy eating.

    Science.gov (United States)

    Sproesser, Gudrun; Klusmann, Verena; Schupp, Harald T; Renner, Britta

    2015-07-01

    The present study investigated people's perception of their own as compared to their peers' healthy eating and related these perceptions to actual healthy eating, BMI, and subsequent healthy eating behavior. Data were collected within the framework of the longitudinal cohort study Konstanz Life Study (T1: N = 770; T2: N = 510). Our results demonstrated an optimistic bias on the group level. Specifically, people rated their own eating behavior as healthier on average than that of their average peers. This comparative optimism occurred even when actual healthy eating was unfavorable and BMI was high. However, it increased with actual healthy eating behavior. Importantly, optimistic perceptions were positively related to the intention to eat healthily and healthy eating six months later. Hence, the results suggest that an optimistic comparative view of one's own healthy eating is grounded in reality and boosts rather than deters subsequent health behavior. This implies that there might not be a need to reduce optimistic perceptions of healthy eating behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Healthy Bones at Every Age

    Science.gov (United States)

    .org Healthy Bones at Every Age Page ( 1 ) Bone health is important at every age and stage of life. The skeleton is our body’s storage bank for ... are many things we can do at every age to keep our bones strong and healthy. Peak ...

  10. Monoclonal antibody:the corner stone of modern biotherapeutics%Monoclonal antibody: the corner stone of modern biotherapeutics

    Institute of Scientific and Technical Information of China (English)

    XIA Zhi-nan; CAI Xue-ting; CAO Peng

    2012-01-01

    Worldwide sales of biologic drugs exceeded 100 billion USD in 2011.About 32% is from therapeutic monoclonal antibody (mAb).With many blockbuster biopharmaceutical patents expiring over the next decade,there is a great opportunity for biosimilar to enter the worldwide especially emerging market.Both European Medicines Agency (EMA) and Food and Drug Administration (FDA) have introduced regulatory frameworks for the potential approval of biosimilar mAb therapeutics.Rather than providing a highly abbreviated path,as in the case for small molecule chemical drug,approval for biosimilar mAb will require clinical trial and the details will be very much on a case-by-case basis.Since mAb is the dominant category of biologic drugs,mAb will be the focus of this review.First,the United States (US) and European Union (EU) approved mAb and those in phase 3 trials will be reviewed,then strategies on how to win biosimilar competition will be reviewed.

  11. Belimumab: anti-BLyS human monoclonal antibody, anti-BLyS monoclonal antibody, BmAb, human monoclonal antibody to B-lymphocyte stimulator.

    Science.gov (United States)

    2008-01-01

    Belimumab is a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, or BLyS. Belimumab is in phase III trials for the treatment of systemic lupus erythematosus (SLE) and has completed a phase II trial in rheumatoid arthritis (RA); the product may also have potential in the treatment of other autoimmune disorders. In May 2001, Cambridge Antibody Technology (now MedImmune) completed its discovery programme and Human Genome Sciences identified belimumab as a candidate for clinical development. More than 1000 distinct human antibodies specific to BLyS were characterized by the collaboration.B-lymphocyte stimulator is a naturally occurring protein discovered by Human Genome Sciences that stimulates B-lymphocytes to develop into mature B cells. Laboratory studies have indicated that higher than normal levels of B-lymphocyte stimulator may contribute to the pathogenesis of autoimmune diseases, such as SLE and RA. Human Genome Sciences (HGS) and Cambridge Antibody Technology signed a collaborative agreement in August 1999 to study the B-lymphocyte stimulator as a human protein target. HGS is also developing other BLyS products. In March 2000, HGS and Cambridge Antibody Technology expanded their agreement into a 10-year collaboration and product development alliance, providing Human Genome Sciences with the right to use the antibody technology of Cambridge Antibody Technology to fully develop human antibodies for therapeutic and diagnostic purposes. Cambridge Antibody Technology will receive royalty payments on product sales from HGS, as well as the development and milestone payments it has already received. Belimumab will be manufactured in Human Genome Sciences' manufacturing facility, located in Rockville, MD, USA. HGS holds commercial rights to the drug. In July 2005, GlaxoSmithKline (GSK) exercised its co-development and co-promotion option to belimumab. In an agreement made in June 1996, HGS had

  12. Quantification of tissue inhibitor of metalloproteinases 2 in plasma from healthy donors and cancer patients

    DEFF Research Database (Denmark)

    Larsen, M. B.; Stephens, R. W.; Brünner, Nils;

    2005-01-01

    and optimized for measurement of TIMP-2 in plasma. The capturing antibody in the ELISA was a monoclonal, while the detecting antibody was a chicken polyclonal antibody recognizing the native form of human TIMP-2. The levels of TIMP-2 were measured in ethylenediaminetetraacetic acid (EDTA) and citrate plasma...... from healthy donors. The median values were determined as 163 ng/ml (n = 186) with a range of 109-253 ng/ml for EDTA plasma and 139 ng/ml (n = 77) with a range of 95-223 ng/ml for citrate plasma. The TIMP-2 concentration in citrate plasma from 15 patients with advanced, stage IV breast cancer had...... a median value of 160 ng/ml, only slightly higher but statistically distinguishable from the level found in citrate plasma from the healthy donors. In addition, the TIMP-2 concentration in EDTA plasma from colorectal cancer patients revealed a significantly higher level in plasma from patients with Dukes...

  13. Use of radiolabeled monoclonal antibodies for diagnostic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Endo, Keigo (Kyoto Univ. (Japan). Faculty of Medicine)

    1990-08-01

    Monoclonal antibodies (MoAbs) are expected to carry radionuclides selectively to target tissues and to offer antigen-specific diagnosis. Indium (In)-111 has many favorable nuclear properties and is efficiently labeled with MoAbs using DAPA as a bifunctional chelating agent. In-111 labeled MoAbs are clinically employed for the diagnosis of malignant melanoma, colorectal cancer and acute myocardial infarction in Japan. Although non-specific deposit of In-111 was seen in liver and bone-marrow, scintigraphy using In-111 labeled MoAbs was encouraging, since it detected about 80% of tumors, tumors missed by conventional diagnostic methods such as CT, and tumors in patients with normal serum CEA values, and acute myocarditis as well as acute myocardial infarction was positive with In-111 labeled Fab fraction of anti-myosin Ab. Acute or subacute toxicity was not observed. Human anti-murine antibody (HAMA) was detected in 53 of 64 (82.8%) patients who were intravenously administered with 20 to 42 mg of anti-melanoma or anti-CEA MoAbs (whole IgG). In contrast, only 5 of 406 (1.2%) patients had detectable levels of HAMA in their serum after receiving 0.5 mg of Fab fraction of MoAb. Recently mouse-human chimeric Ab has been produced by recombinant DNA techniques, which localized well in xenografted tumors and seems to be promising for clinical use. Investigations are under way to increase the tumor to non-tumor ratio by modifying chelating agents for coupling MoAbs with radionuclides. (author).

  14. Monoclonal antibodies against human granulocytes and myeloid differentiation antigens.

    Science.gov (United States)

    Mannoni, P; Janowska-Wieczorek, A; Turner, A R; McGann, L; Turc, J M

    1982-12-01

    Monoclonal antibodies (MCA) were obtained by immunizing BALB/c mice with 99% pure granulocytes from normal donors or with a whole leukocyte suspension obtained from a chronic myelogenous leukemia (CML) patient, and then fusing the mouse spleen cells with a 315-43 myeloma cell clone. Four MCA were selected and studied using ELISA, immunofluorescence, cytotoxicity assays, and FACS analysis. Antibodies 80H.1, 80H.3, and 80H.5 (from normals) and 81H.1 (from CML) detected antigens expressed on neutrophils. Antibodies 80H.1 and 80H.3 (IgG) also reacted with monocytes but not with other blood cell subsets. Antibodies 80H.5 and 81H.1 (IgM) were cytotoxic and reacted strongly with most of the cells of the neutrophil maturation sequence, i.e., myeloblasts, promyelocytes, myelocytes, and mature granulocytes. Antibodies 80H.5 and 81H.1 also inhibited CFU-GM growth stimulated by leukocyte feeder layers or placental conditioned media, but did not inhibit BFU-E and CFU-E. Antigens recognized by 80H.3, 80H.5, and 81H.1 were expressed both on a proportion of cells from HL.60, KG.1, ML.1, and K562 myeloid cell lines, and on a proportion of blast cells isolated from patients with acute myelogenous leukemia. They were not found on lymphoid cell lines or lymphoid leukemia cells. These MCA recognize either late differentiation antigens expressed on mature neutrophils and monocytes (80H.1 and 80H.3) or early differentiation antigens (80H.5 and 81H.1) specific to the granulocytic lineage. They may be useful for a better definition of those antigens specific to hematopoietic stem cells and their relationship with normal or neoplastic hematopoiesis.

  15. Characterization of monoclonal antibodies that strongly inhibit Electrophorus electricus acetylcholinesterase.

    Science.gov (United States)

    Remy, M H; Frobert, Y; Grassi, J

    1995-08-01

    In this study, we describe three different monoclonal antibodies (mAbs Elec-403, Elec-408, and Elec-410) directed against Electrophorus electricus acetylcholinesterase (AChE) which were selected as inhibitors for this enzyme. Two of these antibodies (Elec-403 and Elec-410), recognized overlapping but different epitopes, competed with snake venom toxin fasciculin for binding to the enzyme, and thus apparently recognized the peripheral site of AChE. In addition, the binding of Elec-403 was antagonized by 1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide (BW284C51) and propidium, indicating that the corresponding epitope encompassed the anionic site involved in the binding of these low-molecular-mass inhibitors. The third mAb (Elec-408), was clearly bound to another site on the AChE molecule, and its inhibitory effect was cumulative with those of Elec-403, Elec-410, and fasciculin. All mAbs bound AChE with high affinity and were as strong inhibitors with an apparent Ki values less than 0.1 nM. Elec-403 was particularly efficient with an inhibitory activity similar to that of fasciculin. Inhibition was observed with both charged (acetylthiocholine) and neutral substrates (o-nitrophenyl acetate) and had the characteristics of a non-competitive process. Elec-403 and Elec-410 probably exert their effect by triggering allosteric transitions from the peripheral site to the active site. The epitope recognized by mAb Elec-408 has not been localized, but it may correspond to a new regulatory site on AChE.

  16. Characterization of monoclonal antibodies to avian Escherichia coli Iss.

    Science.gov (United States)

    Lynne, Aaron M; Foley, Steven L; Nolan, Lisa K

    2006-09-01

    Colibacillosis accounts for annual multimillion dollar losses in the poultry industry, and control of this disease is hampered by limited understanding of the virulence mechanisms used by avian pathogenic Escherichia coli (APEC). Previous work in our laboratory has found that the presence of the increased serum survival gene (iss) is strongly associated with APEC but not commensal E. coli, making iss and the protein it encodes (Iss) candidate targets of colibacillosis-control procedures. Previously, we produced monoclonal antibodies (MAbs) against Iss to be used as a reagent in studies of APEC virulence and colibacillosis pathogenesis. Unfortunately, the utility of these MAbs was limited because these MAbs exhibited nonspecific binding. It was thought that the lack of specificity might be related to the fact that these MAbs were of the immunoglobulin M (IgM) isotype. In the present study, new MAbs were produced using a different immunization strategy in an effort to generate MAbs of a different isotype. Also, because Iss bears strong similarity to Bor, a lambda-derived protein that occurs commonly among E. coli, MAbs were assessed for their ability to distinguish Iss and Bor. For these studies, the bor gene from an APEC isolate was cloned into an expression vector. The fusion protein expressed from this construct was used to assess the potential of the anti-Iss MAbs produced in the past and present studies to distinguish Bor and Iss. The MAbs produced in this study were of the IgG1 isotype, which appeared to bind more specifically to Iss than previously generated antibodies in certain immunologic procedures. These results suggested that the MAbs generated in this study might prove superior to the previous MAbs as a reagent for study of APEC. However, both MAbs recognized recombinant Iss and Bor, suggesting that any results obtained using anti-Iss MAbs would need to be interpreted with this cross-reactivity in mind.

  17. Generation and applications of monoclonal antibodies for livestock production.

    Science.gov (United States)

    Van Der Lende, T

    1994-01-01

    Monoclonal antibodies (MCAs) have found widespread applications in livestock production. Although the generation of murine MCAs is at present a routine, the production of homologous MCAs, especially important for in vivo applications, is still hampered by the lack of efficient homologous fusion partners for immortalization of antibody producing lymphocytes of livestock species. At present, MCAs are used in immunodiagnostic tests e.g. to monitor livestock reproduction and quality of livestock products. In the future MCAs will also be used in immunosensors for real-time and on-site applications in the same areas. The commercial application of MCAs for the immunomodulation of (pharmacologically induced) physiological processes underlying important (re)production traits is at present limited to the use of anti-PMSG MCAs in PMSG-induced superovulation. However, many potentially interesting applications are under investigation (e.g. immunopotentiation of growth hormone to enhance growth; immunocytolysis of adipocytes to increase lean meat production; immunoneutralization of GnRH for immunocastration; immunoimitation of hormone activity with anti-idiotype antibodies). Attempts to use specific MCAs for the sexing of embryos have been disappointing, mainly because of the relatively low accuracy. In the future, MCAs against membrane proteins which are specific for X- or Y-chromosome bearing spermatozoa might be used for bulk separation of livestock sperm. In general, it is expected that engineered (homologous) recombinant MCAs will largely contribute to the development of a new generation of rapid immunodiagnostic tests and effective immunomodulation applications. They will further increase the use of MCAs in livestock production.

  18. Human Monoclonal Antibodies Broadly Neutralizing against Influenza B Virus

    Science.gov (United States)

    Yasugi, Mayo; Kubota-Koketsu, Ritsuko; Yamashita, Akifumi; Kawashita, Norihito; Du, Anariwa; Sasaki, Tadahiro; Nishimura, Mitsuhiro; Misaki, Ryo; Kuhara, Motoki; Boonsathorn, Naphatsawan; Fujiyama, Kazuhito; Okuno, Yoshinobu; Nakaya, Takaaki; Ikuta, Kazuyoshi

    2013-01-01

    Influenza virus has the ability to evade host immune surveillance through rapid viral genetic drift and reassortment; therefore, it remains a continuous public health threat. The development of vaccines producing broadly reactive antibodies, as well as therapeutic strategies using human neutralizing monoclonal antibodies (HuMAbs) with global reactivity, has been gathering great interest recently. Here, three hybridoma clones producing HuMAbs against influenza B virus, designated 5A7, 3A2 and 10C4, were prepared using peripheral lymphocytes from vaccinated volunteers, and were investigated for broad cross-reactive neutralizing activity. Of these HuMAbs, 3A2 and 10C4, which recognize the readily mutable 190-helix region near the receptor binding site in the hemagglutinin (HA) protein, react only with the Yamagata lineage of influenza B virus. By contrast, HuMAb 5A7 broadly neutralizes influenza B strains that were isolated from 1985 to 2006, belonging to both Yamagata and Victoria lineages. Epitope mapping revealed that 5A7 recognizes 316G, 318C and 321W near the C terminal of HA1, a highly conserved region in influenza B virus. Indeed, no mutations in the amino acid residues of the epitope region were induced, even after the virus was passaged ten times in the presence of HuMAb 5A7. Moreover, 5A7 showed significant therapeutic efficacy in mice, even when it was administered 72 hours post-infection. These results indicate that 5A7 is a promising candidate for developing therapeutics, and provide insight for the development of a universal vaccine against influenza B virus. PMID:23408886

  19. Antibodies in infectious diseases: polyclonals, monoclonals and niche biotechnology.

    Science.gov (United States)

    Berry, Jody D; Gaudet, Ryan G

    2011-09-01

    Antibody preparations have a long history of providing protection from infectious diseases. Although antibodies remain the only natural host-derived defense mechanism capable of completely preventing infection, as products, they compete against inexpensive therapeutics such as antibiotics, small molecule inhibitors and active vaccines. The continued discovery in the monoclonal antibody (mAb) field of leads with broadened cross neutralization of viruses and demonstrable synergy of antibody with antibiotics for bacterial diseases, clearly show that innovation remains. The commercial success of mAbs in chronic disease has not been paralleled in infectious diseases for several reasons. Infectious disease immunotherapeutics are limited in scope as endemic diseases necessitate active vaccine development. Also, the complexity of these small markets draws the interest of niche companies rather than big pharmaceutical corporations. Lastly, the cost of goods for mAb therapeutics is inherently high for infectious agents due to the need for antibody cocktails, which better mimic polyclonal immunoglobulin preparations and prevent antigenic escape. In cases where vaccine or convalescent populations are available, current polyclonal hyperimmune immunoglobulin preparations (pIgG), with modern and highly efficient purification technology and standardized assays for potency, can make economic sense. Recent innovations to broaden the potency of mAb therapies, while reducing cost of production, are discussed herein. On the basis of centuries of effective use of Ab treatments, and with growing immunocompromised populations, the question is not whether antibodies have a bright future for infectious agents, but rather what formats are cost effective and generate safe and efficacious treatments to satisfy regulatory approval. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Characterization of monoclonal antibodies against waterfowl parvoviruses VP3 protein

    Directory of Open Access Journals (Sweden)

    Yin Xiuchen

    2012-11-01

    Full Text Available Abstract Background The VP3 protein of goose parvovirus (GPV or Muscovy duck parvovirus (MDPV, a major structural protein, can induce neutralizing antibodies in geese and ducks, but monoclonal antibodies (MAbs against VP3 protein has never been characterized. Results Three hybridoma cell lines secreting anti-GPV VP3 MAbs were obtained and designated 4A8, 4E2, and 2D5. Immunoglobulin subclass tests differentiated them as IgG2b (4A8 and 4E2 and IgG2a (2D5. Dot blotting assays showed that three MAbs reacted with His-VP3 protein in a conformation-independent manner. A competitive binding assay indicated that the MAbs delineated two epitopes, A and B of VP3. Immunofluorescence assay showed that MAbs 4A8, 4E2, and 2D5 could specifically bind to goose embryo fibroblast cells (GEF or duck fibroblast cells (DEF infected with GPV and MDPV. Dot blotting also showed that the MAbs recognized both nature GPV and MDPV antigen. Western blotting confirmed that the MAbs recognized VP3 proteins derived from purified GPV and MDPV particles. The MAbs 4A8 and 2D5 had universal reactivity to heterologous GPV and MDPV tested in an antigen-capture enzyme-linked immunosorbent assay. Conclusions Preparation and characterization of these the MAbs suggests that they may be useful for the development of a MAb-capture ELISA for rapid detection of both GPV and MDPV. Virus isolation and PCR are reliable for detecting GPV and MDPV infection, but these procedures are laborious, time-consuming, and requiring instruments. These diagnosis problems highlight the ongoing demand for rapid, reproducible, and automatic methods for the sensitive detection of both GPV and MDPV infection.