Sample records for circulating anti-bpl antibodies

  1. Semiquantitative determination of circulating islet cell surface antibodies in diabetes

    Circulating pancreatic islet cell antibodies have been demonstrated in patients with insulin-dependent diabetes (IDD). The islet cell surface antibodies (ICSA) were determined by an indirect immunofluorescence test using a suspension of viable islet cells, and similar cytoplasmic antibodies which require the use of group O human pancreas were also found in the serum of some patients. A strong association exists between the presence of islet cell antibodies and the onset of insulin-dependent diabetes. The quantitative determination of circulating ICSA using 125I-protein A, which binds to IgG attached to the islet cell surface, was essentially as described by Lernmark et al. In the present study, we determined the circulating ICSA in diabetes, especially in IDD. The ICSA were estimated in various sera from both indirect immunofluorescence and 125I-protein A. Controls bound 125I-protein A. Sera from 4 IDD patients with circulating ICSA demonstrated by immunofluorescence showed >3,000 cpm 125I-protein A binding activity, and that from 5 patients without ICSA bound <2,000 cpm. Sera from newly-diagnosed diabetics who had severe hyperglycemia showed <2,000 cpm, with or without ICSA. (author)

  2. A new sensitive immunosorbent radioassay for the detection of circulating antibodies to polypeptide hormones and proteins

    A solid-phase immunosorbent radioassay for the detection of circulating antibodies to protein hormones is described. The assay is based on the binding of the homologous 125I-labelled antigen to the antibodies which are then bound to anti-IgG antibodies covalently coupled to Sepharose. It can easily be applied as a complement to any radioimmunoassay for the detection of circulating antibodies to the ligand measured. The assay system avoids falsely elevated values due to interference of high serum concentrations of the antigen. The assay was applied to measure antibodies to FSH, LH, TSH, GH, prolactin, insulin and thyroglobulin (Tg). Among patients with chronic thyroiditis Tg antibodies were found in 100% of the sera. In diffuse toxic goitre 73% of the patients had detectable Tg antibodies. Insulin antibodies were present in 82% of the sera from patients with insulin treated diabetes. No antibodies were found against the other protein hormones tested. (author)

  3. Does Circulating Antibody Play a Role in the Protection of Piglets against Porcine Epidemic Diarrhea Virus?

    Poonsuk, Korakrit; Giménez-Lirola, Luis Gabriel; Zhang, Jianqiang; Arruda, Paolo; Chen, Qi; Correa da Silva Carrion, Lucas; Magtoto, Ronaldo; Pineyro, Pablo; Sarmento, Luciana; Wang, Chong; Sun, Yaxuan; Madson, Darin; Johnson, John; Yoon, Kyoung-Jin; Zimmerman, Jeffrey


    The contribution of circulating antibody to the protection of naïve piglets against porcine epidemic diarrhea virus (PEDV) was evaluated using a passive antibody transfer model. Piglets (n = 62) derived from 6 sows were assigned to one of 6 different treatments using a randomized block design which provided for allocation of all treatments to all sows' litters. Each treatment was designed to achieve a different level of circulating anti-PEDV antibody via intraperitoneally administration of co...

  4. Immunoradiometric assay for the detection of circulating antibodies to murine monoclonal antibodies in humans (HAMA)

    The increasing clinical use of monoclonal antibodies (MAb) has focussed attention on the importance of the generation of human anti-mouse antibodies (HAMA). HAMA can not only be life threatening but can also be associated with reduced image quality and accelerated MAb clearance in vivo as well as interfere with in vitro MAb based assays. The development of a two step immunoradiometric assay (IRMA) for detecting circulating HAMA is reported. Preliminary results have been generated with specific MAb coated polystyrene wells. The appropriately diluted serum sample is first incubated with the MAb coated wells followed by a wash step and a second incubation with 125I labeled goat anti-human IgG. After a final wash, the wells are assayed for 125I and the results expressed as percent of the input bound. The prototype assay is compared with an existing commercially available ELISA kit using patient sera obtained at various time periods up to 7 months after IV MAb injection for radioimmunoscintigraphy. 18 refs., 2 tabs., 1 fig

  5. Circulating antibodies against faecal bacteria assessed by immunomorphometry: combining quantitative immunofluorescence and image analysis.

    Apperloo-Renkema, H.Z.; Wilkinson, M. H. F.; van der Waaij, D


    A new technique to study the prevalence of circulating antibodies directed against different morphological groups ('morphotypes') of bacteria in fresh faeces is presented. The technique combines quantitative indirect immunofluorescence with digital image analysis. Plasma antibody titres and patterns of IgA, IgG and IgM isotype against morphotypes of faecal bacteria were determined in ten healthy individuals.

  6. ACE inhibitors can induce circulating antibodies directed to antigens of the superficial epidermal cells.

    Cozzani, Emanuele; Rosa, Gian Marco; Drosera, Massimo; Intra, Chiara; Barsotti, Antonio; Parodi, Aurora


    Drug-induced pemphigus has been reported in patients receiving angiotensin-converting enzyme inhibitors. The aim of this work was to study a group of hypertensive patients without skin diseases treated with angiotensin-converting enzyme (ACE) Inhibitors (I), to verify the presence of serum circulating anti-antibodies. The indirect immunofluorescence showed that 33 sera (52.38%) presented autoantibodies directed to an antigen of the cytoplasm of the superficial epidermal keratinocytes. Two of the 33 positive sera had antibodies to Dsg1 and/or 3 in ELISA. Immunoblot analyses were negative. All the 48 control sera were found to have no circulating antibodies using the three assays. Our results would confirm that ACEI drugs may trigger the production of circulating autoantibodies also in patients without clinical manifestations of pemphigus. PMID:20563876

  7. Influence of circulating antigen on blood pool activity of a radioiodinated monoclonal antibody

    Athymic mice with and without circulating CA 125 antigen were injected with 0.1-100 μg of 131I-labeled OC 125 F(ab')2 antibody fragment. Both the blood clearance of 131I activity and the change in serum CA 125 were monitored over 24 h. Influence of CA 125 on blood pool activity could be avoided only at the 100 μg dose. In patient studies, circulating CA 125 levels decreased for the first 2 h after injection of OC 125 F(ab')2 but generally returned to preinjection levels shortly thereafter. In vitro binding studies using the sera from patients injected with 131I-labeled OC 125 F(ab')2 suggest that circulating CA 125 could interfere with the tumor uptake of the labeled antibody. (author)

  8. CD133 antibody conjugation to decellularized human heart valves intended for circulating cell capture.

    Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony


    The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases. PMID:26333364

  9. Affinity isolation of antigen-specific circulating B cells for generation of phage display-derived human monoclonal antibodies

    Ditzel, Henrik


    A method is described for affinity isolation of antigen-specific circulating B cells of interest for subsequent generation of immune antibody phage display libraries. This approach should overcome the problem of low yields of monoclonal antibodies of interest in the libraries generated from...... the frequency of antibody phage particles of interest in the library and allow for efficient isolation monoclonal antibodies with the predefined specificity....

  10. Antibodies against "DANGER" in the dynamic of post-transplant circulation.

    Taniguchi, Michiko


    Evidence that has accumulated about the impact of non-human leukocyte antigen (HLA) antibodies against tissue-restricted antigens supports the concept that humoral targets can be constantly altered by transplant-associated stresses such as ischemia-reperfusion (IR) injury, organ preservation, immunosuppressive drugs, and pre-existing diseases. This accounts for the growing interest in "danger" signals--in the form of damage-induced molecules--expanding our understanding of the humoral cause of allograft rejection and failure from thinking it is caused only by genetically determined HLA mismatches to seeing the role played by antibody recognition of antigens modified posttransplant. The heterogeneous repertoire of antibodies was evidenced by the recent protein microarray analysis that revealed increased posttransplant levels of heterogeneous antibodies against the targets localized in specific kidney compartments. Antibodies can also be developed against molecules dynamically generated in the circulation as damage-associated molecular patterns (DAMPs) that are the endogenous version of exogenous pathogen-associated molecular patterns (PAMPs). Antibodies against some DAMP molecules have been identified in many autoimmune diseases, but mostly have been elusive in transplant immunology. Those humoral DAMP targets include the well-studied high-mobility group box 1, IR injury-induced proteins, and oxidation-specific epitopes exposed on oxidized low-density lipoprotein. Moreover, understanding the intersection of endogenous DAMPs and exogenous PAMPs in transplant immunology may reveal a new aspect of humoral reactions. Recently reported cross-recognition by polyreactive antibodies of apoptotic cells may be one of many unidentified recognition patterns that indicate existence of an immune system strategy for defending against a number of stress-induced targets as a set of "danger." Given all these findings, the recent approach of identifying disease-specific panels of up

  11. Comparisons of the effect of naturally acquired maternal pertussis antibodies and antenatal vaccination induced maternal tetanus antibodies on infant's antibody secreting lymphocyte responses and circulating plasma antibody levels.

    Ahmad, Shaikh Meshbahuddin; Alam, Jahangir; Afsar, Nure Alam; Huda, Nazmul; Kabir, Yearul; Qadri, Firdausi; Raqib, Rubhana; Stephensen, Charles B


    The goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy. Infants received tetanus and pertussis vaccines at 6, 10 and 14 wk of age. TT and PT anti-IgG secretion by infant lymphocytes was measured at 15 wk. Plasma antibodies were measured at 6 wk (pre-vaccination), 15 wk and 1 y of age. Prior to vaccination, TT and PT antibody were detected in 94.6% and 15.2% of infants. At 15 wk anti-TT-IgG and anti-PT-IgG in plasma was increased by 7-9 fold over pre-vaccination levels, while at 1 y plasma anti-TT-IgG was decreased by approximately 5-fold from the peak and had returned to near the pre-vaccination level. At 1 y plasma anti-PT-IgG was decreased by 2-fold 1 yfrom the 15 wk level. However, 89.5% and 82.3% of infants at 1 y had protective levels of anti-TT and anti-PT IgG, respectively. Pre-vaccination plasma IgG levels were associated with lower vaccine-specific IgG secretion by infant lymphocytes at 15 wk (p < 0.10). This apparent inhibition was seen for anti-TT-IgG at both 15 wk (p < 0.05) and t 1 y (p < 0.10) of age. In summary, we report an apparent inhibitory effect of passively derived maternal antibody on an infants' own antibody response to the same vaccine. However, since the cut-off values for protective titers are low, infants had protective antibody levels throughout infancy. PMID:27176823

  12. Immunocapture of circulating Schistosoma mansoni cathepsin B antigen (Sm31) by anti-Sm31 polyclonal antibodies.

    González, Amelia Y; Sulbarán, Guidenn S; Ballen, Diana E; Cesari, Italo M


    Adult Schistosoma mansoni parasites have the capacity to degrade ingested host hemoglobin and other host plasma proteins by using a series of gut proteolytic enzymes, including cathepsin B; this enzyme is released to the host intravascular environment during regurgitations of adult worms. Cathepsin B becomes thus a circulating parasite component that has been shown to be specifically recognized as the Sm31 antigen by antibodies present in most S. mansoni infected patients. Taking advantage of this immunological property, we attempted here to immunocapture Sm31 from sera of infected patients using specific polyclonal rabbit antibodies raised against a highly enriched preparation of Sm31 and detect its intrinsic proteolytic activity using a previously described solid-phase procedure called Cysteine Protease Immuno Assay (CPIA). To produce highly specific anti-Sm31/cathepsin B antibodies, cathepsin B (Sm31 or SmCB) was enriched more than 3000-folds from an adult worm preparation using a series of conventional biochemical steps including ion exchange and affinity chromatography. Anti-cathepsin B antibodies were generated by immunizing rabbits with the enriched cathepsin B fraction; these antibodies recognized a band of Mr.~31kDa in Western-blot (WB) analysis of this fraction and were able to capture, in a modified CPIA procedure, Sm31/SmCB present in sera from infected Venezuelan patients living in low endemic areas for schistosomiasis. CPIA showed 100% sensitivity and 100% specificity; representing a new diagnostic tool to detect circulating Sm31 antigen in actual infections. PMID:26709076

  13. A Case of Simultaneous, Biopsy-Proven, Classic, ANCA-Positive Wegener's Granulomatosis and Anti-GBM Disease, but without Detectible Circulating Anti-GBM Antibodies

    Aleksandra Gmurczyk; Shubhada N. Ahya; Robert Goldschmidt; George Kim; L. Tammy Ho; Kevin Nash


    Wegener's granulomatosis (WG) is a systemic, necrotizing, granulomatous vasculitis of unknown etiology. Approximately 75% of cases present as classic WG with both pulmonary and renal involvement, while the remaining 25% of patients present with a limited form with either predominantly upper or lower respiratory tract symptoms. Ninety percent of WG patients have circulating anti–neutrophil cytoplasmic antibodies (ANCA), and approximately 10% have both circulating ANCA antibodies and concomitan...

  14. Solid-phase radioimmunoassay for measurement of circulating antibody titres to wheat gliadin and its subfractions in patients with adult coeliac disease

    Ciclitira, P.J.; Ellis, H.J. (Guy' s Hospital, London (UK)); Evans, D.J. (Hammersmith Hospital, London (UK))


    A solid-phase radioimmunoassay for the measurement of circulating antibody titres to wheat gliadin is described. Using this assay, the authors have measured antibody titres to unfractionated gliadin in normal healthy controls, in coeliac patients on a gluten-free or a normal diet, and in patients with ulcerative colitis and Crohn's disease. High titres of antibodies to unfractionated gliadin were observed only in the patients with untreated coeliac disease. Antibody titres to ..cap alpha.., ..beta.., ..gamma.. and gliadin subfractions were measured in patients with untreated coeliac disease and compared with titres in normal controls. Patients with untreated coeliac disease had higher antibody titres to the gliadin subfractions. No specific pattern of circulating antibody titres to gliadin subfractions was observed in the untreated coeliac patients which would provide a diagnostic profile. These results suggest shared antigenicity between the gliadin subfractions.

  15. A solid-phase radioimmunoassay for measurement of circulating antibody titres to wheat gliadin and its subfractions in patients with adult coeliac disease

    A solid-phase radioimmunoassay for the measurement of circulating antibody titres to wheat gliadin is described. Using this assay, the authors have measured antibody titres to unfractionated gliadin in normal healthy controls, in coeliac patients on a gluten-free or a normal diet, and in patients with ulcerative colitis and Crohn's disease. High titres of antibodies to unfractionated gliadin were observed only in the patients with untreated coeliac disease. Antibody titres to α, #betta#, #betta# and #betta# gliadin subfractions were measured in patients with untreated coeliac disease and compared with titres in normal controls. Patients with untreated coeliac disease had higher antibody titres to the gliadin subfractions. No specific pattern of circulating antibody titres to gliadin subfractions was observed in the untreated coeliac patients which would provide a diagnostic profile. These results suggest shared antigenicity between the gliadin subfractions. (Auth.)

  16. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S;


    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known...... inverse correlation between DNA concentration and anti-dsDNA antibodies may reflect antibody-dependent deposition of immune complexes during the development of lupus nephritis in autoimmune lupus prone mice. The measurement of circulating DNA in SLE sera by using qPCR may indicate and detect the...... development of lupus nephritis at an early stage....

  17. Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

    Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

  18. Radiolabeled monoclonal antibodies. Development of a new method to remove circulating activity - diagnostic applications and implications for therapy

    The aim of this thesis was to develop and investigate the usefulness of extracorporeal immunoadsorption (ECIA) to remove circulating activity after the localization of radiolabeled monoclonal antibodies to tumors. A compartment model, based on the biokinetics of 125I-labeled antibodies 96.5 was developed to estimate the effect of ECIA on the tumor-to-normal tissue ratios. ECIA was simulated at different times after injection of the antibodies and the calculations showed an increased diagnostic ratio for several hours after the ECIA procedure, and that an enhancement of the therapeutic ratio was possible. These results led to the development of animal models where the ECIA could be evaluated and the biokinetic behaviour of different radiolabeled monoclonal antibodies investigated with and without the application of ECIA. A general ECIA method, based on biotinylated antibodies and an avidin agarose column as adsorbent, was developed. Studies in tumor bearing nude rats showed that ECIA enhanced of the tumor-to-normal tissue activity ratios by a factor of 4 for the liver, kidneys and bone marrow. For the L6 antibody, the image contrast of tumors localized in one kidney of the rats, was increased from 1.1 to 1.6. A software anthropomorphic phantom was used in Monte Carlo simulations of clinically realistic scintillation camera image acquisition. The effect of ECIA on the contrast enhancement and on the detectability of simulated tumors located centrally in the liver was studied. The contrast increased linearly with an increasing tumor/liver ratio. The contrast was higher for SPECT than for planar images and a contrast of 1.15 required a tumor/liver activity ratio of 1.9 for SPECT and 4.5 for planar images. ECIA in combination with SPECT imaging of radiolabeled antibodies has a great potential in increasing the detectability of tumors. These studies have shown the possibility with ECIA to increase the contrast in radioimmunoimaging and to enhance the therapeutic ratio

  19. Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy

    P53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma. Serum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted. Twenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT. Anti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population

  20. Antibody

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

  1. Serological detection of circulating Angiostrongylus vasorum antigen and specific antibodies in dogs from central and northern Italy.

    Guardone, L; Schnyder, M; Macchioni, F; Deplazes, P; Magi, M


    The most frequently employed method for the diagnosis of Angiostrongylus vasorum in dogs is the detection of first stage larvae (L1) in faeces. The sensitivity of coproscopy, however, is limited in case of low parasite load, intermittent larval excretion, and during pre-patency. An epidemiological survey on dogs was conducted applying serological methods in two Italian regions where angiostrongylosis is endemic in foxes. 265 dog serum samples from Tuscany (central Italy - site A) and 447 from Liguria (north-western Italy - site B) were tested with a sandwich-ELISA for detection of circulating antigen, and with an ELISA using A. vasorum adult somatic antigen purified by monoclonal antibodies for specific antibody detection. During previous examinations dogs naturally infected with Leishmania infantum (n=149), Dirofilaria immitis (n=40), Dirofilaria repens (n=30), Acanthocheilonema reconditum (n=27), Crenosoma vulpis (n=1), A. vasorum (n=2), Capillaria aerophila (n=35), Capillaria boehmi (n=3), Toxocara canis (n=68), Toxascaris leonina (n=5), hookworms (n=37) and Trichuris vulpis (n=39) were detected. Sera of these dogs were used to evaluate cross reactions. In site A, 2 dogs (0.8%) were seropositive for antibody and antigen detection and 4 (1.5%) for antibody detection only. From site B, 4 dogs (0.9%) were seropositive for both tests, while other 4 dogs (0.9%) for antigen detection only and 9 dogs (2%) for antibody detection only. Considering a subgroup of 347 dogs from site B which had also been tested with the Baermann technique, 2 (0.6%) were positive for both tests, 4 (1.2%) for antigen detection only and 9 (2.6%) for antibody detection only. The two dogs which were positive for both serological tests were also positive for A. vasorum L1 in the faeces. No significant difference in seropositivities was observed in the group of dogs with other proven parasitic infections. A. vasorum serology presents significant advantages (diagnosis before patency, single serum

  2. Circulating Visfatin in Hypothyroidism Is Associated with Free Thyroid Hormones and Antithyroperoxidase Antibodies

    Nadia Sawicka-Gutaj


    Full Text Available We hypothesized that regulation of visfatin in hypothyroidism might be altered by coexisting chronic autoimmune thyroiditis. This is a prospective case-control study of 118 subjects. The autoimmune study group (AIT consisted of 39 patients newly diagnosed with hypothyroidism in a course of chronic autoimmune thyroiditis. The nonautoimmune study group (TT consisted of 40 patients thyroidectomized due to the differentiated thyroid cancer staged pT1. The control group comprised 39 healthy volunteers adjusted for age, sex, and BMI with normal thyroid function and negative thyroid antibodies. Exclusion criteria consisted of other autoimmune diseases, active neoplastic disease, diabetes mellitus, and infection, which were reported to alter visfatin level. Fasting blood samples were taken for visfatin, TSH, free thyroxine (FT4, free triiodothyronine (FT3, antithyroperoxidase antibodies (TPOAb, antithyroglobulin antibodies (TgAb, glucose, and insulin levels. The highest visfatin serum concentration was in AIT group, and healthy controls had visfatin level higher than TT (p=0.0001. Simple linear regression analysis revealed that visfatin serum concentration was significantly associated with autoimmunity (β=0.1014; p=0.003, FT4 (β=0.05412; p=0.048, FT3 (β=0.05242; p=0.038, and TPOAb (β=0.0002; p=0.0025, and the relationships were further confirmed in the multivariate regression analysis.

  3. Combined Serological Detection of Circulating Angiostrongylus vasorum Antigen and Parasite-specific Antibodies in Dogs from Hungary.

    Schnyder, Manuela; Schaper, Roland; Lukács, Zoltán; Hornok, Sándor; Farkas, Róbert


    The occurrence of the nematode Angiostrongylus vasorum, also known as the French heartworm, is increasingly being reported from various European countries. The adults of this parasite species live in the pulmonary arteries and right cardiac ventricle of wild canids and domestic dogs. Larval stages and eggs in the lungs induce inflammatory verminous pneumonia, causing severe respiratory disease in dogs. Furthermore, haematological and neurological signs and even death may occur. In Hungary, A. vasorum has been identified in red foxes, golden jackals and in two dogs and some slugs. In this first large-scale survey, 1247 sera from pet dogs were collected and tested by an ELISA for the detection of circulating antigen of A. vasorum and by a separate ELISA to detect specific antibodies against the parasite. A total of 1.36% (n = 17, 95 % confidence intervals, CI: 0.80 - 2.17 %) of the animals were positive in both ELISAs, while 1.76 % (n = 22, CI: 1.11 - 2.66 %) of the tested dogs were antigen-positive only and 2.73 % (n = 34, CI: 1.90 - 3.79 %) were positive for specific antibodies only. Regions with antigen- and antibody-positive animals overlapped and were distributed over nearly the whole sampled areas of the country. A considerable number of cases was observed in Budapest and also in the southern part of the country bordering Croatia, while in the most eastern part bordering Ukraine no positive samples were detected. These results confirm the endemic occurrence of A. vasorum in dogs originating from different parts of Hungary and the significant advantages of A. vasorum serology in epidemiological studies. PMID:26152415

  4. Functional meaning of scintigraphic and echographic patterns, and of circulating anti-peroxidase antibodies in asymptomatic chronic thyroiditis

    Rubello, D.; Gasparoni, P. [Hospital of Castelfranco Veneto, Treviso, (Italy). Endocrinology Service; Rota, G.; Borsato, N.; Zanco, P.; Chierichetti, F.; Ferlin, G. [Hospital of Castelfranco Veneto, Treviso, (Italy). Nuclear Medicine Service


    Asymptomatic chronic thyroiditis (ACT) is a variant of the autoimmune thyroiditis characterized by the presence of circulating anti-thyroid antibodies and the absence of palpable goiter. Thyroid function can be normal but a considerable percentage of ACT patients tend to develop subclinical hypothyroidism over time and thus periodical controls of thyroid hormones and TSH levels are needed. At present, useful parameters for predicting the functional out-came of ACT patients are lacking. To investigate this aspect, the authors evaluated 57 consecutive ACT patients (51 females, 6 males, aged 22-56 years) by means of thyroid {sup 99m}Tc-pertechnetate scintigraphy and echography, and by measuring the serum level of anti-peroxidase antibodies (TPOAbs), FT4, T3 and TSH. At first observation, 30 patients were euthyroid whereas 27 had subclinical hypothyroidism. No patient had been previously treated with thyroid hormones. Thyroid scan showed a normal pattern or a diffuse and mild irregular uptake, without differences between euthyroid and subclinical hypothyroid patients. TPOAb levels tend to be higher in patients with subclinical hypothyroidism in comparison to the euthyroid patients (5893{+-}1423 and 3943{+-}912 UI/mL, respectively) but the difference was not statistically significant by using Student`s {sup t-}test. Echography showed a normal pattern in 14 patients, while a diffuse hypoechoic pattern in the other cases, mild in 12, moderate in 19 and marked in 12, as found. A significantly higher prevalence of subclinical hypothyroidism was observed in the group of patients with a moderate or marked hypoechoic pattern in comparison to the group with a normo-echoic or mild hypoechoic pattern (70.4% versus 23.0%, Fisher`s exact test p=0.00003). Furthermore, the 3 patients who developed thyroid failure during a one-year follow-up also presented a moderate or marked hypoechoic pattern. (Abstract Truncated)

  5. UV activation of polymeric high aspect ratio microstructures: ramifications in antibody surface loading for circulating tumor cell selection.

    Jackson, Joshua M; Witek, Małgorzata A; Hupert, Mateusz L; Brady, Charles; Pullagurla, Swathi; Kamande, Joyce; Aufforth, Rachel D; Tignanelli, Christopher J; Torphy, Robert J; Yeh, Jen Jen; Soper, Steven A


    The need to activate thermoplastic surfaces using robust and efficient methods has been driven by the fact that replication techniques can be used to produce microfluidic devices in a high production mode and at low cost, making polymer microfluidics invaluable for in vitro diagnostics, such as circulating tumor cell (CTC) analysis, where device disposability is critical to mitigate artifacts associated with sample carryover. Modifying the surface chemistry of thermoplastic devices through activation techniques can be used to increase the wettability of the surface or to produce functional scaffolds to allow for the covalent attachment of biologics, such as antibodies for CTC recognition. Extensive surface characterization tools were used to investigate UV activation of various surfaces to produce uniform and high surface coverage of functional groups, such as carboxylic acids in microchannels of different aspect ratios. We found that the efficiency of the UV activation process is highly dependent on the microchannel aspect ratio and the identity of the thermoplastic substrate. Colorimetric assays and fluorescence imaging of UV-activated microchannels following EDC/NHS coupling of Cy3-labeled oligonucleotides indicated that UV-activation of a PMMA microchannel with an aspect ratio of ~3 was significantly less efficient toward the bottom of the channel compared to the upper sections. This effect was a consequence of the bulk polymer's damping of the modifying UV radiation due to absorption artifacts. In contrast, this effect was less pronounced for COC. Moreover, we observed that after thermal fusion bonding of the device's cover plate to the substrate, many of the generated functional groups buried into the bulk rendering them inaccessible. The propensity of this surface reorganization was found to be higher for PMMA compared to COC. As an example of the effects of material and microchannel aspect ratios on device functionality, thermoplastic devices for the

  6. The effect of circulating antigen on the biodistribution of the engineered human antibody hCTM01 in a nude mice model

    Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but did not shed into the circulation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver uptake of the secreting cell line. (orig.). With 4 figs., 1 tab

  7. Electrophoresis and electro-affinity transfer with specific antibodies to alpha-fetoprotein for detection of circulating immune complexes of alpha-fetoprotein.



    Full Text Available A combination of agarose gel electrophoresis and a newly developed technique of electro-affinity transfer was applied to the detection of circulating immune complexes of human alpha-fetoprotein (AFP and anti-AFP. After electrophoretic transfer to nitrocellulose membrane, to which affinity-purified polyclonal horse antibodies to human AFP were bound, the membranes were treated with or without rabbit immunoglobulins to human AFP, followed by overlaying with horseradish peroxidase-labeled goat anti-rabbit IgG for color development. Artificial complexes formed in vitro from human AFP and rabbit anti-AFP were clearly separated from free AFP by the agarose electrophoresis. The complexes were stained 20-40% as dark as the equivalent amount of free AFP by treatment with rabbit anti-AFP, and 10-20% as dark without the antibody treatment over a wide range of antigen-antibody ratios.

  8. Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens.

    Shigeta, Mika; Saiki, Minoru; Tsuruta, Daisuke; Ohata, Chika; Ishii, Norito; Ono, Fumitake; Hamada, Takahiro; Dainichi, Teruki; Furumura, Minao; Zone, John J; Karpati, Sarolta; Sitaru, Cassian; Hashimoto, Takashi


    Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten-sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme-linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti-endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten-sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten-sensitive enteropathy and no DH-specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH. PMID:22963165

  9. Circulating microRNA expression pattern separates patients with anti-neutrophil cytoplasmic antibody-associated vasculitis from healthy controls

    Skoglund, C.; Carlsen, A.; Weiner, M.;


    Objective. Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) has an unpredictable course and better biomarkers are needed. Micro-RNAs in body fluids are protected from degradation and might be used as biomarkers for diagnosis and prognosis, here we explore the potential in AAV...

  10. Heterogeneous detection of circulating tumor cells in patients with colorectal cancer by immunomagnetic enrichment using different EpCAM-specific antibodies

    Büchler Markus W


    Full Text Available Abstract Background Circulating tumor cells (CTC and disseminated tumor cells (DTC are thought to be responsible for metastasis, so the detection of CTC may serve as individual prognostic factor in patients suffering from colorectal cancer. Therefore, a series of immunomagnetic enrichment methods for CTC have been developed using a variety of monoclonal antibodies against the Epithelial Cell Adhesion Molecule (EpCAM. However, it remains unclear whether all commercially available EpCAM antibodies show the same sensitivity and specificity. Furthermore, it remains unclear which method of sample preparation and cell extraction is most suitable for immunomagnetic enrichment and detection of CTC. In this study, we aimed to investigate whether the detection of CTC by a cytokeratin 20 reverse transcriptase-polymerase chain reaction (CK20 RT-PCR may be influenced by the use of various Epithelial Cell Adhesion Molecule (EpCAM antibodies for immunomagnetic isolation of CTC. Results Using both EpCAM antibodies (mAb BerEP4 and mAb KS1/4 for immunomagnetic enrichment in blood samples of 39 patients with colorectal cancer we found heterogenous results in each patient with regard to tumor cell detection. In the tumor cell spiking experiments with whole blood samples the sensitivity of the CK 20 RT-PCR assay was higher using immunomagnetic beads coated with mAb KS1/4 compared to precoated mAb BerEP4 Dynabeads. Extraction of MNC fraction with Ficoll gradient centrifugation prior to immunomagnetic enrichment resulted in a higher sensitivity of the CK 20 RT-PCR assay. Conclusions We concluded that isolation and detection of CTC with immunomagnetic enrichment methods is critically dependent on the used EpCAM clone. Further studies with a larger number of patients should clarify if the enrichment protocol influences the prognostic value of the tumor cell detection protocol.

  11. UV activation of polymeric high aspect ratio microstructures: ramifications in antibody surface loading for circulating tumor cell selection†

    Jackson, Joshua M.; Witek, Małgorzata A.; Hupert, Mateusz L.; Brady, Charles; Pullagurla, Swathi; Kamande, Joyce; Aufforth, Rachel D.; Tignanelli, Christopher J.; Torphy, Robert J.; Yeh, Jen Jen; Soper, Steven A.


    The need to activate thermoplastic surfaces using robust and efficient methods has been driven by the fact that replication techniques can be used to produce microfluidic devices in a high production mode and at low cost, making polymer microfluidics invaluable for in vitro diagnostics, such as circulating tumor cell (CTC) analysis, where device disposability is critical to mitigate artifacts associated with sample carryover. Modifying the surface chemistry of thermoplastic devices through ac...

  12. Pregnancy in a Patient With Primary Membranous Nephropathy and Circulating Anti-PLA2R Antibodies: A Case Report.

    Al-Rabadi, Laith; Ayalon, Rivka; Bonegio, Ramon G; Ballard, Jennifer E; Fujii, Alan M; Henderson, Joel M; Salant, David J; Beck, Laurence H


    There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A2 receptor (PLA2R), the major autoantigen in primary MN. We present what we believe to be the first known case of successful pregnancy in a 39-year-old woman with PLA2R-associated MN. In the year prior to pregnancy, the patient developed anasarca, hypoalbuminemia (albumin, 1.3-2.2g/dL), and proteinuria (protein excretion, 29.2g/d). Kidney biopsy revealed MN with staining for PLA2R, and the patient was seropositive for anti-PLA2R autoantibodies. She did not respond to conservative therapy and was treated with intravenous rituximab (2 doses of 1g each). Several weeks after presentation, she was found to be 6 weeks pregnant and was closely followed up without further immunosuppressive treatment. Proteinuria remained with protein excretion in the 8- to 12-g/d range. Circulating anti-PLA2R levels declined but were still detectable. At 38 weeks, a healthy baby girl was born, without proteinuria at birth or at her subsequent 6-month postnatal visit. At the time of delivery, the mother still had detectable circulating anti-PLA2R of immunoglobulin G1 (IgG1), IgG3, and IgG4 subclasses, although at low titers. Only trace amounts of IgG4 anti-PLA2R were found in cord blood. Potential reasons for the discrepancy between anti-PLA2R levels in the maternal and fetal circulation are discussed. PMID:26744127

  13. Detection of Antibodies Secreted from Circulating Mycobacterium tuberculosis-Specific Plasma Cells in the Diagnosis of Pediatric Tuberculosis▿

    Raqib, Rubhana; Mondal, Dinesh; Karim, M. Anwarul; Chowdhury, Fahima; Ahmed, Sultan; Luby, Stephen; Cravioto, Alejandro; Andersson, Jan; Sack, David


    Diagnosis of tuberculosis (TB) in children is difficult because symptoms are often nonspecific or absent in infected children, diagnostic specimens are difficult to obtain from younger children, and >50% have negative TB cultures. Thus, there is an urgent need for improved diagnosis of pediatric TB. This study aimed to evaluate the diagnostic value of a new serological method, the ALS (antibodies in lymphocyte supernatant) assay, for the diagnosis of active TB in children with clinically iden...

  14. Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis

    Fismen, S; Hedberg, A; Fenton, K A;


    Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo...... (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i...... were present in capillary lumina in glomeruli and skin of all nephritic individuals. Thus, chromatin-IgG complexes accounting for lupus nephritis seem to reach skin through circulation, but other undetermined factors are required for these complexes to deposit within skin membranes....

  15. Immunodiagnosis of Fasciola gigantica Infection Using Monoclonal Antibody-Based Sandwich ELISA and Immunochromatographic Assay for Detection of Circulating Cathepsin L1 Protease.

    Panat Anuracpreeda

    Full Text Available Tropical fasciolosis caused by Fasciola gigantica infection is one of the major diseases infecting ruminants in the tropical regions of Africa and Asia including Thailand. Parasitological diagnosis of fasciolosis is often unreliable and possesses low sensitivity. Therefore, the detection of circulating parasite antigens is thought to be a better alternative for diagnosis of fasciolosis, as it reflects the real parasite burden.In this study, we have produced a monoclonal antibody (MoAb against recombinant F. gigantica cathepsin L1 (rFgCatL1, and developed both sandwich enzyme-linked immunosorbent assay (sandwich ELISA and immunochromatographic (IC test for rapid detection of circulating cathepsin L1 protease (CatL1 in the sera from mice experimentally and cattle naturally infected with Fasciola gigantica. MoAb 4E3 and biotinylated rabbit anti-recombinant CatL1 antibody were selected due to their high reactivities and specificities.The lower detection limits of sandwich ELISA and IC test were 3 pg/ml and 0.256 ng/ml, respectively. Sandwich ELISA and IC test could detect F. gigantica infection from day 1 to 35 post infection. In experimental mice, the sensitivity, specificity and accuracy were 95%, 100% and 98.6% (for sandwich ELISA, and 93%, 100% and 98.2% (for IC test, while in natural cattle they were 98.3%, 100% and 99.5% (for sandwich ELISA, and 96.7%, 100% and 99.1% (for IC test.These two assay methods showed high efficiencies and precisions for diagnosis of fasciolosis by F. gigantica.

  16. Modulation of circulating protein biomarkers following TRC105 (anti-endoglin antibody) treatment in patients with advanced cancer

    Liu, Yingmiao; Starr, Mark D.; Brady, John C; Dellinger, Andrew; Pang, Herbert; Adams, Bonne; Theuer, Charles P.; Lee, Nam Y.; Hurwitz, Herbert I.; Nixon, Andrew B.


    TRC105 is an endoglin-targeting drug that possesses anti-angiogenic and antitumor potential. Analysis of the initial phase I trial of TRC105 demonstrated good tolerability and efficacy in cancer patients. In this report, we analyzed multiple circulating biomarkers at baseline, cycle 2 day 1 (C2D1), and end of study (EOS) for each patient. The baseline level and the fold change from baseline to both C2D1 and EOS for each marker were statistically analyzed. At C2D1, seven markers were significa...

  17. Existence of circulating anti-endothelial cell antibodies after heart transplantation is associated with post-transplant acute allograft rejection.

    Lehle, Karla; Kroher, Johannes; Kolat, Philipp; von Süßkind-Schwendi, Marietta; Schmid, Christof; Haneya, Assad; Rupprecht, Leopold; Hirt, Stephan


    Anti-endothelial cell antibodies (AECA) may be involved in the development of heart allograft rejection. Its detection might be a cheap and noninvasive method to identify high-risk patients. An indirect immunofluorescence method on human umbilical vein endothelial cells was used to investigate the presence of AECAs in 260 pre- and post-transplant serum samples sequentially collected from 34 patients within the first year after heart transplantation (HTX). The presence of AECAs before (23.5 %) and early after HTX (14.7 %) was associated with a significantly increased risk of early acute rejection (75 and 60 %, respectively) compared to 33 % in AECA-negative patients (p = 0.049). Moreover, rejections from AECA-positive patients were more severe (p = 0.057) with a significantly increased incidence of multiple (p = 0.025). The mean number of the sum of rejection episodes was significantly higher in AECA-positive patients (p ≤ 0.05). Patients free of AECAs mainly received mycophenolate mofetil as primary immunosuppression (p = 0.067). Nevertheless, the presence of AECAs did not affect long-term outcome and mortality of HTX patients. Despite a low number of patient samples, the detection of AECAs before and early after HTX could be used as a biomarker for an increased risk of early acute rejection in high-risk patients. This easy method might be a valuable tool to support screening procedures to improve individualized immunosuppressive therapy. PMID:25820657

  18. Modulation of circulating protein biomarkers following TRC105 (anti-endoglin antibody) treatment in patients with advanced cancer.

    Liu, Yingmiao; Starr, Mark D; Brady, John C; Dellinger, Andrew; Pang, Herbert; Adams, Bonne; Theuer, Charles P; Lee, Nam Y; Hurwitz, Herbert I; Nixon, Andrew B


    TRC105 is an endoglin-targeting drug that possesses anti-angiogenic and antitumor potential. Analysis of the initial phase I trial of TRC105 demonstrated good tolerability and efficacy in cancer patients. In this report, we analyzed multiple circulating biomarkers at baseline, cycle 2 day 1 (C2D1), and end of study (EOS) for each patient. The baseline level and the fold change from baseline to both C2D1 and EOS for each marker were statistically analyzed. At C2D1, seven markers were significantly downregulated (angiopoietin-2 [Ang-2], insulin-like growth factor-binding protein-3 [IGFBP-3], plasminogen activator inhibitor-1 [PAI-1] total, platelet-derived growth factor [PDGF]-AA, PDGF-BB, thrombospondin-1 [TSP-1], and vascular endothelial growth factor [VEGF]-D). Meanwhile, seven markers were upregulated by C2D1 (E-Cadherin, soluble Endoglin [sEnd], E-Selectin, interleukin-6 [IL-6], osteopontin [OPN], TSP-2, and von Willebrand factor [vWF]). At EOS, seven markers were upregulated including Ang-2, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), IGFBP-1, IL-6, TSP-2, and vascular cell adhesion molecule-1 (VCAM-1). A statistical trend was also seen for increases of VEGF-A and placenta growth factor (PlGF) at EOS. Throughout treatment, sEnd levels significantly increased, an observation that was recapitulated in cultured endothelial cells. This is the first report of plasma-based biomarkers in patients receiving TRC105. TRC105 treatment by C2D1 was associated with decreases in several angiogenic factors, including Ang-2, PDGF isoforms, and VEGF isoforms, offering insight into the mechanisms underlying TRC105's anti-angiogenic, antitumor function. Increases in sEnd were the most significant of all observed biomarker changes and may reflect direct drug effects. Additionally, biomarker changes in response to TRC105 are distinct from those seen in patients treated with VEGF-targeting drugs, suggesting the possible utility of combining these two classes

  19. Modulation of circulating protein biomarkers following TRC105 (anti-endoglin antibody) treatment in patients with advanced cancer

    TRC105 is an endoglin-targeting drug that possesses anti-angiogenic and antitumor potential. Analysis of the initial phase I trial of TRC105 demonstrated good tolerability and efficacy in cancer patients. In this report, we analyzed multiple circulating biomarkers at baseline, cycle 2 day 1 (C2D1), and end of study (EOS) for each patient. The baseline level and the fold change from baseline to both C2D1 and EOS for each marker were statistically analyzed. At C2D1, seven markers were significantly downregulated (angiopoietin-2 [Ang-2], insulin-like growth factor-binding protein-3 [IGFBP-3], plasminogen activator inhibitor-1 [PAI-1] total, platelet-derived growth factor [PDGF]-AA, PDGF-BB, thrombospondin-1 [TSP-1], and vascular endothelial growth factor [VEGF]-D). Meanwhile, seven markers were upregulated by C2D1 (E-Cadherin, soluble Endoglin [sEnd], E-Selectin, interleukin-6 [IL-6], osteopontin [OPN], TSP-2, and von Willebrand factor [vWF]). At EOS, seven markers were upregulated including Ang-2, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), IGFBP-1, IL-6, TSP-2, and vascular cell adhesion molecule-1 (VCAM-1). A statistical trend was also seen for increases of VEGF-A and placenta growth factor (PlGF) at EOS. Throughout treatment, sEnd levels significantly increased, an observation that was recapitulated in cultured endothelial cells. This is the first report of plasma-based biomarkers in patients receiving TRC105. TRC105 treatment by C2D1 was associated with decreases in several angiogenic factors, including Ang-2, PDGF isoforms, and VEGF isoforms, offering insight into the mechanisms underlying TRC105's anti-angiogenic, antitumor function. Increases in sEnd were the most significant of all observed biomarker changes and may reflect direct drug effects. Additionally, biomarker changes in response to TRC105 are distinct from those seen in patients treated with VEGF-targeting drugs, suggesting the possible utility of combining these two

  20. The role of circulating anti-p53 antibodies in patients with advanced non-small cell lung cancer and their correlation to clinical parameters and survival

    Lung cancer causes approximately one million deaths each year worldwide and protein p53 has been shown to be involved in the intricate processes regulating response to radiation and/or chemotherapeutic treatment. Consequently, since antibodies against p53 (anti-p53 antibodies) are associated with mutations within the p53 gene it seems likely that these antibodies could, hypothetically, be correlated with prognosis. Serum samples from patients with non-small cell lung cancer (NSCLC) admitted to the Department of Oncology, University Hospital, Uppsala, Sweden, during 1983–1996 were studied. Anti-p53 abs were measured using a sandwich ELISA (Dianova, Hamburg, Germany). The present study included 84 patients with stage IIIA-IV (advanced NSCLC). At least three serum samples from each patient were collected and altogether 529 serum samples were analysed for the presence of anti-p53 antibodies. The median value of anti-p53 antibodies was 0.06 (range 0 – 139.8). Seventeen percent of investigated NSCLC first serum samples (n = 84) expressed elevated levels of anti-p53 antibodies. Anti-p53 antibodies were not correlated to tumour volume or platelets. Survival analysis showed that anti-p53 antibodies were not associated with survival as revealed by univariate analysis (p = 0.29). However, patients with adenocarcinoma had a significantly poorer survival if they expressed anti-p53 antibodies (p = 0.01), whereas this was not found for patients with squamous cell carcinoma (p = 0.13). In patients where the blood samples were collected during radiation therapy, a statistically significant correlation towards poorer survival was found (p = 0.05) when elevated anti-p53 antibodies levels were present. No correlations to survival were found for serum samples collected prior to radiation therapy, during chemotherapy, or during follow-up. When anti-p53 antibodies were measured continuously, no increase in median anti-p53 values was observed the closer the individual patient come to

  1. Effects of tumour mass and circulating antigen on the biodistribution of 111In-labelled F(ab')2 fragments of human prostatic acid phosphatase monoclonal antibody in nude mice bearing PC-82 human prostatic tumor xenografts

    We have evaluated the effects of tumour mass and circulating antigen (prostatic acid phosphatase, PAP) on the biodistribution and the incorporation of 111In-labelled F(ab')2 monoclonal antibody (MoAb) fragments directed against human PAP into human prostatic tumours (PC-82; 0.1-8.9 g) growing in nude mice. The radioactivities in the blood, liver, spleen, kidney and tumour were compared at 1, 3, 4 and 6 days after the intravenous administration of the antibody fragments. There was a significant correlation between the tumour size and the serum PAP concentration in the model employed. Even tissue of a small tumour (111In-labelled F(ab')2 fragments. This relationship had levelled off by 72 h and most likely reflected a better vascularisation of the smaller tumours. Our results show that the increase in tumour size and in the concentration of circulating antigen in the blood led to decreased tumour-to-blood ratios, since there was a tendency for higher blood activities in mice with larger tumours and higher serum PAP concentrations. There was no correlation between tumour size and label uptake by the liver during the follow-up over 144 h, although serum PAP concentrations ranged from 3.1 μg/l to 352 μg/l. On the other hand, when compared with our previous data obtained with non-tumour-bearing mice, there was a significant increase in the uptake by the liver and spleen. These results indicate that even a small concentration of circulating antigen was able to trigger an abnormal change in the biodistribution of MoAbs. (orig.)

  2. 基于IgY的ELISA用于囊尾蚴循环抗原的检测%Detecting the circulating antigen(CA) of Taenia solium cysticercosis with specific egg yolk antibody (IgY) by sandwich ELISA

    刘玉; 王元伦; 唐雨德


    Objective To develop a sensitive and specific double antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect circulating antigen (CA) of Taeniasoliumcysticercosis with chicken egg yolk immunoglobulin antibodies (IgY).Methods Hens were subcutaneously immunized with CA and the crude IgY was extracted from egg yolk by water dilution method.A sandwich ELISA had been developed by purified IgY antibodies as capture antibody and monoclonal antibodies labeled with peroxidase as detecting antibody.The detection limits of CA were analyzed.The sera and cerebrospinal fluid of patients,the sera of healthy people,sick pigs and healthy pigs were detected in parallel by the established ELISA methods.It's sensitivity and specificity were evaluated by comparison with ELISA based monoclonal antibodies.Results The minimal detectable concentration of CA was 8.3 and 13.9 μg/ml by sandwich ELISA based IgY and monoclonal antibodies,respectively.The positive rates of samples from 139 patients,19 cerebrospinal fluid of patients and 222 sick pigs were 100% (139/139),89.5% (17/19) and 100% (222/222) by sandwich ELISA based IgY respectively.The negative rates of samples from 50 healthy people and 20 healthy pigs were 100%.Conclusion The novel double-antibody sandwich ELISA using anti-CA IgY appears to be sensitive and specific for detection the CA of Taenia solium cysticercosis.It is the promising assay for immunodiagnosis of Taenia solium cysticercosis.%目的 建立基于IgY的双抗体夹心ELISA用于囊尾蚴病的诊断.方法 制备并纯化抗囊尾蚴循环抗原(CA)卵黄抗体(IgY),建立以抗CA的IgY为捕获抗体,酶标记抗CA的单克隆抗体1A5为检测抗体的双抗体夹心ELISA法,共检测样品450份,并与捕获抗体和检测抗体均为单克隆抗体的ELISA法比较,验证方法的敏感性、特异性与实用性.结果 成功制备并鉴定了特异性IgY抗体,建立了基于Igy的双抗体夹心ELISA检测体系.IgY-ELISA和双单

  3. Fetal Circulation

    ... Pressure High Blood Pressure Tools & Resources Stroke More Fetal Circulation Updated:Jul 8,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  4. Monoclonal antibodies and cancer

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111In, 67Ga and 131I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  5. Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies

    Weissenstein Ulrike


    Full Text Available Abstract Background Circulating tumor cells (CTCs are detectable in peripheral blood of metastatic breast cancer patients (MBC. In this paper we evaluate a new CTC separation method based on a combination of anti-EpCAM- and anti-cytokeratin magnetic cell separation with the aim to improve CTC detection with low target antigen densities. Methods Blood samples of healthy donors spiked with breast cancer cell line HCC1937 were used to determine accuracy and precision of the method. 10 healthy subjects were examined to evaluate specificity. CTC counts in 59 patients with MBC were measured to evaluate the prognostic value on overall survival. Results Regression analysis of numbers of recovered vs. spiked HCC1937 cells yielded a coefficient of determination of R2 = 0.957. The average percentage of cell recovery was 84%. The average within-run coefficient of variation for spiking of 185, 85 and 30 cells was 14%. For spiking of 10 cells the within-run CV was 30%. No CTCs were detected in blood of 10 healthy subjects examined. A standard threshold of 5 CTC/7.5 ml blood as a cut-off point between risk groups led to a highly significant prognostic marker (p  Conclusions We show that our CTC detection method is feasible and leads to accurate and reliable results. Our data suggest that a refined differentiation between patients with different CTC levels is reasonable.

  6. Thyroid Antibodies

    ... be limited. Home Visit Global Sites Search Help? Thyroid Antibodies Share this page: Was this page helpful? Also known as: Thyroid Autoantibodies; Antithyroid Antibodies; Antimicrosomal Antibody; Thyroid Microsomal Antibody; ...

  7. Lung Circulation.

    Suresh, Karthik; Shimoda, Larissa A


    The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed. © 2016 American Physiological Society. Compr Physiol 6:897-943, 2016. PMID:27065170

  8. Antigenic analysis of classical swine fever virus E2 glycoprotein using pig antibodies identifies residues contributing to antigenic variation of the vaccine C-strain and group 2 strains circulating in China

    Peng Jinrong


    Full Text Available Abstract Background Glycoprotein E2, the immunodominant protein of classical swine fever virus (CSFV, can induce neutralizing antibodies and confer protective immunity in pigs. Our previous phylogenetic analysis showed that subgroup 2.1 viruses branched away from subgroup 1.1, the vaccine C-strain lineage, and became dominant in China. The E2 glycoproteins of CSFV C-strain and recent subgroup 2.1 field isolates are genetically different. However, it has not been clearly demonstrated how this diversity affects antigenicity of the protein. Results Antigenic variation of glycoprotein E2 was observed not only between CSFV vaccine C-strain and subgroup 2.1 strains, but also among strains of the same subgroup 2.1 as determined by ELISA-based binding assay using pig antisera to the C-strain and a representative subgroup 2.1 strain QZ-07 currently circulating in China. Antigenic incompatibility of E2 proteins markedly reduced neutralization efficiency against heterologous strains. Single amino acid substitutions of D705N, L709P, G713E, N723S, and S779A on C-strain recombinant E2 (rE2 proteins significantly increased heterologous binding to anti-QZ-07 serum, suggesting that these residues may be responsible for the antigenic variation between the C-strain and subgroup 2.1 strains. Notably, a G713E substitution caused the most dramatic enhancement of binding of the variant C-strain rE2 protein to anti-QZ-07 serum. Multiple sequence alignment revealed that the glutamic acid residue at this position is conserved within group 2 strains, while the glycine residue is invariant among the vaccine strains, highlighting the role of the residue at this position as a major determinant of antigenic variation of E2. A variant Simpson's index analysis showed that both codons and amino acids of the residues contributing to antigenic variation have undergone similar diversification. Conclusions These results demonstrate that CSFV vaccine C-strain and group 2 strains

  9. Antibodies to human fetal erythroid cells from a nonimmune phage antibody library

    Huie, Michael A.; Cheung, Mei-Chi; Muench, Marcus O.; Becerril, Baltazar; Kan, Yuet W.; Marks, James D.


    The ability to isolate fetal nucleated red blood cells (NRBCs) from the maternal circulation makes possible prenatal genetic analysis without the need for diagnostic procedures that are invasive for the fetus. Such isolation requires antibodies specific to fetal NRBCs. To generate a panel of antibodies to antigens present on fetal NRBCs, a new type of nonimmune phage antibody library was generated in which multiple copies of antibody fragments are displayed on each pha...

  10. Antithyroid microsomal antibody

    Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also been linked to an increased risk ...

  11. Circulation economics

    Ingebrigtsen, Stig; Jakobsen, Ove


    Purpose - This paper is an attempt to advance the critical discussion regarding environmental and societal responsibility in economics and business. Design/methodology/approach - The paper presents and discusses as a holistic, organic perspective enabling innovative solutions to challenges...... concerning the responsible and efficient use of natural resources and the constructive interplay with culture. To reach the goal of sustainable development, the paper argues that it is necessary to make changes in several dimensions in mainstream economics. This change of perspective is called a turn towards...... presupposes a perspective integrating economic, natural and cultural values. Third, to organize the interplay between all stakeholders we introduce an arena for communicative cooperation. Originality/value - The paper concludes that circulation economics presupposes a change in paradigm, from a mechanistic...

  12. A radioimmunoprecipitation polyethylene glycol assay for circulating Entamoeba histolytica antigens

    An assay capable of detecting circulating Entamoeba histolytica antigens in amoebiasis is described. This assay utilised a radiolabelled affinity purified rabbit anti-E. histolytica antibody that had been depleted of antibodies that cross-react with human serum proteins, and a polyethylene glycol precipitation step. (Auth.)

  13. Radioimmunoprecipitation polyethylene glycol assay for circulating Entamoeba histolytica antigens

    Pillai, S.; Mohimen, A.; Mehra, S. (Calcutta Medical Research Inst., Calcutta (India). Kothari Centre of Gastroenterology)


    An assay capable of detecting circulating Entamoeba histolytica antigens in amoebiasis is described. This assay utilised a radiolabelled affinity purified rabbit anti-E. histolytica antibody that had been depleted of antibodies that cross-react with human serum proteins, and a polyethylene glycol precipitation step.

  14. Treatment with depleting CD4 monoclonal antibody results in a preferential loss of circulating naive T cells but does not affect IFN-gamma secreting TH1 cells in humans

    Rep, M.H.G.; Oosten, van, J.M.F.; Roos, M T; Adér, H.J.; Polman, C H; Lier, van, R.


    CD4(pos) TH1 T cells are considered to play a central role in a number of human autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis. Experimental treatment protocols aimed at selectively eliminating CD4(pos) T cells thus far have yielded disappointing clinical results. Here we analyzed phenotype and function of circulating T cells in multiple sclerosis patients treated with the chimeric CD4 mAb cM-T412 in a randomized, double-blind, placebo-controlled, magnetic resona...

  15. Pharmacological selection of antibodies for immunoscintigraphy

    The recent development of hybridoma technology has resulted in the production of monoclonal antibodies that recognize a variety of tumor antigens. Many antibodies have been developed and some of them are used with different success in clinical practice. A list of criteria is proposed for the selection of antibodies suitable for imaging studies illustrated with the example of two monoclonal antibodies anti-CEA and 19.9 used in colorectal carcinoma imaging. Monoclonal antibodies obtained today are not truly tumor-specific, they are tumor-associated; this suggests that some cross-reactions with normal tissues exist. For immunoscintigraphical use it is important to select antibodies which procedure high tumor cell staining with limited reactivity against normal tissues. Antibodies can be separated into F(ab')2 and Fab fragments which diffuse more easily into the tumor with a rapid clearance from the circulation giving higher tumor to normal tissues ratio at an early time. Antibodies with both high affinity and avidity towards tumor cell receptors produce better imaging results. Antibodies can be labelled directly with iodine or technetium and with indium using chelating agents. In vivo kinetics of radiolabelled antibodies are very different considering the nuclide and the labelling method used. Pharmacokinetics on nude mice grated with human tumors are very useful for selecting the most appropriate nuclide antibody fragment and the most efficient labelling technique for a given application. (author)

  16. Antibody therapy for Ebola

    Qiu, Xiangguo; Kobinger, Gary P


    Ebola viruses can cause severe hemorrhagic fever in humans and nonhuman primates with fatality rates up to 90%, and are identified as biosafety level 4 pathogens and CDC Category A Agents of Bioterrorism. To date, there are no approved therapies and vaccines available to treat these infections. Antibody therapy was estimated to be an effective and powerful treatment strategy against infectious pathogens in the late 19th, early 20th centuries but has fallen short to meet expectations to widely combat infectious diseases. Passive immunization for Ebola virus was successful in 2012, after over 15 years of failed attempts leading to skepticism that the approach would ever be of potential benefit. Currently, monoclonal antibody (mAbs)-based therapies are the most efficient at reversing the progression of a lethal Ebola virus infection in nonhuman primates, which recapitulate the human disease with the highest similarity. Novel combinations of mAbs can even fully cure lethally infected animals after clinical symptoms and circulating virus have been detected, days into the infection. These new developments have reopened the door for using antibody-based therapies for filovirus infections. Furthermore, they are reigniting hope that these strategies will contribute to better control the spread of other infectious agents and provide new tools against infectious diseases. PMID:24503566

  17. Bispecific antibodies.

    Kontermann, Roland E; Brinkmann, Ulrich


    Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also place targets into close proximity, either to support protein complex formation on one cell, or to trigger contacts between cells. Examples of 'forced-connection' functionalities are bsAbs that support protein complexation in the clotting cascade, or tumor-targeted immune cell recruiters and/or activators. Following years of research and development (R&D), the first bsAb was approved in 2009. Another bsAb entered the market in December 2014 and several more are in clinical trials. Here, we describe the potentials of bsAbs to become the next wave of antibody-based therapies, focusing on molecules in clinical development. PMID:25728220

  18. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Gascoyne, Peter R.C.; Sangjo Shim


    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim...

  19. West Nile Virus Antibodies in Wild Birds, Morocco, 2008

    Figuerola, Jordi; Baouab, Riad E.; Soriguer, Ramón C; Fassi-Fihri, O.; Llorente, Francisco; Jiménez-Clavero, Miguel A.


    To determine circulation of West Nile virus (WNV) during nonepidemic times, we serosurveyed wild birds of Morocco in 2008. We found antibodies against WNV in 12 (3.5%) birds, against Usutu virus in 1 (0.3%), and against both in 2 (0.6%). High WNV prevalence among juvenile birds suggests local virus circulation among resi- dent birds.

  20. Immunoprophylaxis in fish by injection of mouse antibody genes

    Lorenzen, Niels; Cupit, P.M.; Einer-Jensen, Katja; Lorenzen, Ellen; Ahrens, Peter; Secombes, C.J.; Cunningham, C.


    infectious diseases. To test this in a fish model, a gene construct encoding a neutralizing single-chain antibody to the fish-pathogenic rhabdovirus VHSV (viral hemorrhagic septicemia virus) was administered to rainbow trout by intramuscular injection of plasmid DNA, Circulating recombinant antibodies could...

  1. High prevalence of human anti-bovine IgG antibodies as the major cause of false positive reactions in two-site immunoassays based on monoclonal antibodies

    Andersen, Ditte C; Koch, Claus; Jensen, Charlotte H;


    were purified by protein G affinity chromatography from culture supernatant containing 10% (v/v) fetal calf serum (FCS). Human anti-animal IgG (bovine, mouse, horse, and swine) antibodies and human anti-bovine serum albumin antibodies were measured using an ELISA design, with direct bridging of the...... human anti-mouse IgG antibodies (HAMA), described to create false positive results, may be due to a crossreacting fraction of the polyclonal circulating antibodies against bovine IgG....

  2. Microwave circulator design

    Linkhart, Douglas K


    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  3. Monoclonal antibodies

    Monoclonal antibodies (MAbs) are antibodies having single specificity for a given antigen site (epitope). The development of hybridoma technology and the relative ease by which MAbs can be prepared has revolutionized many aspects of serological applications in diagnosis and differentiation of disease producing agents. The property of monospecificity offers advantages in diagnostic applications over polyclonal sera in that tests can be defined exactly with regard to the antigen detected and the affinity of reaction between the given antigenic site and the monoclonal reagent. In addition, MAbs offer better possibilities for test standardization, because the same reagent can be used in different laboratories. Such an MAb can be supplied by a central laboratory or 'grown' from hybridoma cells, ensuring that the resultant product is identical from laboratory to laboratory and that the part of the test involving the MAb reaction is the same. The methodologies for inoculation regimes, mice, cloning methods, selection of fusion partners, etc., have been validated extensively in developed country laboratories. The decision to establish a MAb production facility must be examined on a strict cost-benefit basis, since it is still expensive to produce a product. There are many MAbs available that should be sought to allow exploitation in developing tests. If a production facility is envisaged, it should produce reagents for national needs, i.e. there should be a clear problem oriented approach whereby exact needs are defined. In the field of veterinary applications, MAbs are the central reagent in many immunoassays based on the enzyme linked immunosorbent assay (ELISA). The development of specific tests for diagnosing diseases is dominated by MAbs and has been fuelled by a strong research base, mainly in developed countries allied to developing countries through the study of related diseases. Thus, there are very many assays dependent on MAbs, some of which form the basis of

  4. Passive antibody transfer in chickens to model maternal antibody after avian influenza vaccination

    Maternal antibodies (MAb) may interfere with avian influenza (AI) vaccination. MAb interference prevents an immune response by binding to the vaccine antigen. Once MAb titers are depleted, the chick is susceptible to a circulating AI virus. This study examined the affect of MAb on seroconversion ...

  5. Monoclonal antibodies.


    The ability to produce and exploit monoclonal antibodies (mAbs) has revolutionized many areas of biological sciences. The unique property of an mAb is that it is a single species of immunoglobulin (IG) molecule. This means that the specificity of the interaction of the paratopes on the IG, with the epitopes on an antigenic target, is the same on every molecule. This property can be used to great benefit in immunoassays to provide tests of defined specificity and sensitivity, which improve the possibilities of standardization. The performance of assays can often be determined relating the actual weight of antibody (hence the number of molecules) to the activity. Often the production of an mAb against a specific epitope is the only way that biological entities can be differentiated. This chapter outlines the areas involving the development of assays based on mAbs. The problems involved address include the physical aspects of mAbs and how they may affect assay design and also the implications of results based on monospecific reagents. Often these are not fully understood, leading to assays that are less than satisfactory, which does not justify the relatively high cost of preparing and screening of mAbs. There are many textbooks and reviews dealing with the preparation of mAbs, the principles involved, and various purification and manipulative methods for the preparation of fragments and conjugation. There has been little general information attempting to summarize the best approaches to assay design using mAbs. Much time can be wasted through bad planning, and this is particularly relevant to mAbs. A proper understanding of some basic principles is essential. It is beyond the scope of this chapter to discuss all aspects, but major areas are highlighted. PMID:19219589

  6. Mimivirus Circulation among Wild and Domestic Mammals, Amazon Region, Brazil

    Dornas, Fábio P.; Rodrigues, Felipe P.; Boratto, Paulo V.M.; Silva, Lorena C. F.; Ferreira, Paulo C. P.; Bonjardim, Cláudio A.; Trindade, Giliane S; Kroon, Erna G.; La Scola, Bernard; Abrahão, Jônatas S


    To investigate circulation of mimiviruses in the Amazon Region of Brazil, we surveyed 513 serum samples from domestic and wild mammals. Neutralizing antibodies were detected in 15 sample pools, and mimivirus DNA was detected in 9 pools of serum from capuchin monkeys and in 16 pools of serum from cattle.

  7. Mimivirus circulation among wild and domestic mammals, Amazon Region, Brazil.

    Dornas, Fábio P; Rodrigues, Felipe P; Boratto, Paulo V M; Silva, Lorena C F; Ferreira, Paulo C P; Bonjardim, Cláudio A; Trindade, Giliane S; Kroon, Erna G; La Scola, Bernard; Abrahão, Jônatas S


    To investigate circulation of mimiviruses in the Amazon Region of Brazil, we surveyed 513 serum samples from domestic and wild mammals. Neutralizing antibodies were detected in 15 sample pools, and mimivirus DNA was detected in 9 pools of serum from capuchin monkeys and in 16 pools of serum from cattle. PMID:24564967

  8. Intracellular and circulating neuronal antinuclear antibodies in human epilepsy

    Iffland, Philip H.; Carvalho-Tavares, Juliana; Trigunaite, Abhishek; Man, Shumei; Rasmussen, Peter; Alexopoulos, Andreas; Ghosh, Chaitali; Jørgensen, Trine N.; Janigro, Damir


    There are overwhelming data supporting the inflammatory origin of some epilepsies (e.g., Rasmussen's encephalitis and limbic encephalitis). Inflammatory epilepsies with an autoimmune component are characterized by autoantibodies against membrane-bound, intracellular or secreted proteins (e.g., voltage gated potassium channels). Comparably, little is known regarding autoantibodies targeting nuclear antigen. We tested the hypothesis that in addition to known epilepsy-related autoantigens, human...

  9. Concepts in Assisted Circulation

    Lefemine, Armand A.; Dunbar, Jacob; DeLucia, Anthony


    Assisted circulation by extracorporeal and extracardiac bypass techniques must be based on the requirements of the heart and of the total body, though these may differ. The cardiac problem in cardiogenic shock is more likely to be a biventricular problem demanding decompression of both sides. Extra pulmonary oxygenation should be avoided because of complexity in long-term use. Principles of assisted circulation may be applied in an extra-thoracic temporary manner or as an intracorporeal long-...

  10. Detection of polysaccharide antigens of Candida albicans interfering with specific antibodies in human sera

    A double antibody sandwich radioimmunoassay was developed for the detection of circulating polysaccharide antigens of Candida albicans. The sensitivity of the assay for polysaccharides was 1 ng/mL. The in-vitro interference of specific polysaccharide antibodies, even from sera with low antibody levels, could be demonstrated. The sensitivity of the antigen detection decreased proportionally to the amount of polysaccharide antibodies in the sera. The sensitivity of the assay was almost completely restored by heating the sera. This procedure destroyed antibodies and the released polysaccharide antigens were detectable in the test system by using radiolabelled anti-polysaccharide antibodies. (author)

  11. Gaussian Fibonacci Circulant Type Matrices

    Zhaolin Jiang


    Full Text Available Circulant matrices have become important tools in solving integrable system, Hamiltonian structure, and integral equations. In this paper, we prove that Gaussian Fibonacci circulant type matrices are invertible matrices for n>2 and give the explicit determinants and the inverse matrices. Furthermore, the upper bounds for the spread on Gaussian Fibonacci circulant and left circulant matrices are presented, respectively.

  12. Macrophages are critical effectors of antibody therapies for cancer

    Weiskopf, Kipp; Weissman, Irving L


    Macrophages are innate immune cells that derive from circulating monocytes, reside in all tissues, and participate in many states of pathology. Macrophages play a dichotomous role in cancer, where they promote tumor growth but also serve as critical immune effectors of therapeutic antibodies. Macrophages express all classes of Fcγ receptors, and they have immense potential to destroy tumors via the process of antibody-dependent phagocytosis. A number of studies have demonstrated that macropha...

  13. Antibodies and Selection of Monoclonal Antibodies.

    Hanack, Katja; Messerschmidt, Katrin; Listek, Martin


    Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology. PMID:27236550


    R. Naeije; CHESLER, N


    The pulmonary circulation is a high flow and low pressure circuit, with an average resistance of 1 mmHg.min.L−1 in young adults, increasing to 2.5 mmHg.min.L−1 over 4–6 decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20–25 mmHg threshold associ...

  15. Imaging spectrum of primary antiphospholipid antibody syndrome

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

  16. Imaging spectrum of primary antiphospholipid antibody syndrome

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


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

  17. Antiphospholipid Antibody Syndrome

    ... page from the NHLBI on Twitter. What Is Antiphospholipid Antibody Syndrome? Antiphospholipid (AN-te-fos-fo-LIP-id) antibody ... weeks or months. This condition is called catastrophic antiphospholipid syndrome (CAPS). People who have APS also are at ...

  18. The antibody mining toolbox

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D.; Shen, Xiaohong; Bradbury, Andrew RM; Kiss, Csaba


    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput ...

  19. IgE antibody responses in schistosomiasis measured by a radioallergosorbent test

    Helminth infections are associated with the production of unusually high concentrations of circulating IgE antibody. Assays for IgE antibodies should provide useful approaches for the study of protective immunity and may also be of use in serodiagnosis of diseases induced by helminths. The radioallergosorbent test is carried out by attaching the antigen or allergen to an insoluble supportive material, allowing the IgE antibodies in the test serum to react with excess bound antigen, and then estimating the IgE antibody bound by its reaction with 125I-labelled goat anti-human IgE antibody

  20. Heavy chain only antibodies

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


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

  1. Hepatitis A virus antibody

    A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

  2. Local immunotherapy based on agonistic CD40 antibodies effectively inhibits experimental bladder cancer

    Sandin, Linda C; Tötterman, Thomas H; Sara M. Mangsbo


    Local immunotherapy resurfaces in the field of cancer as a potential way to cure localized and metastatic disease with limited toxic effects. We have recently demonstrated that local administration of agonistic CD40 antibodies can cure localized as well as disseminated bladder neoplasms. This approach reduces the circulating concentrations of antibodies that would result from systemic delivery, hence resulting in limited toxicity.

  3. Clinical experience in humans with radiolabeled antibody for tumor detection

    I-131 and Tc-99m labeled polyclonal or monoclonal antibody and fragments of antibody, specific to human chorionic gonadotropin (hCG) or to a melanoma cell surface antigen (MCSA) were injected into proven cancer patients. Using standard homeostasis parameters, and scanning techniques, the safety and efficacy of each antibody was evaluated. Antibody fragments were expected to clear faster from the circulation allowing for earlier imaging and a better target-to-non-target ratio. The technetium label may perturb the antiboby's kinetics so that clearance is more rapid for both whole antibody and fragments. After a statistical evaluation of all parameters measured pre and post injection it was concluded that no acute toxicity reactions were present in any patient studied. Scan results were not acceptable for a tumor detecting procedure used in routine practice. Tumor upake was seen in less than 10% of scans

  4. Chronic Renal Allograft Dysfunction Antibody-Mediated: An Update

    Maurizio Salvadori,


    Full Text Available This paper reviews the most important studies on chronic antibody-mediated rejection (cABMR, which is an important cause of late graft dysfunction after renal transplantation. Several antibodies seem to be responsible for chronic rejection; new techniques have allowed us to identify these antibodies in circulation. The pathogenetic role of the antibodies generally includes the complement pathway, but may also be complement-independent. This paper also examines the pathogenesis of chronic endothelial lesions, as well as the histopathological aspects. Antibodies responsible for chronic rejection may preexist before transplantation or may develop after transplantation. The possible therapeutic approaches are poor and principally based on early identification and desensitisation techniques. New B cell targeting drugs are aimed at an improved control of the relevant condition.


    Mail Office


    Internal mail envelopes often finish up in large piles in certain offices, thus creating a shortage for other users of the mail service, who would be grateful if everyone with an unused stock could deposit them in their mail box, after attaching them together with an elastic band or a piece of string. The messengers will then collect them so that the Mail Office can put them back in circulation. Thank you for your understanding and collaboration.

  6. Cytolytic antibodies to melanocytes in vitiligo.

    Cui, J; Arita, Y; Bystryn, J C


    Patients with vitiligo have been found to have circulating antibodies to pigment cells. To evaluate the functional activity of these antibodies, a highly sensitive europium release assay was used to compare complement-mediated cytolysis of human melanocytes by sera of 56 patients with vitiligo (20 with active disease, 25 with inactive disease, 11 with unidentified disease activity) and 47 control individuals. Significant melanocyte lysis was mediated by 32 (57%) of the patients with vitiligo but by only three (6%) of the control sera (p < 0.001), and by 17 (85%) of 20 patients with active vitiligo versus 11 (44%) of 25 patients with inactive disease (p < 0.025). Mean melanocyte lysis by vitiligo sera was 24% versus 6% by control sera (p < 0.0001). A subset of 12 vitiligo sera with high titers of cytolytic antibodies to melanocytes (34% mean cytolysis) reacted minimally (< 2% mean cytolysis) to a panel of control cells that included human and murine melanomas, human fibroblasts, lung carcinoma, and rhabdomyosarcoma. These findings indicate that antibodies present in patients with vitiligo have the functional ability to selectively kill melanocytes and are more common in active disease. These observations support, but do not prove, the hypothesis that vitiligo is an autoimmune disease and that anti-pigment cell antibodies have a role in inducing the disease. PMID:8496621

  7. Systemic sclerosis without antinuclear antibodies or Raynaud's phenomenon

    Schneeberger, D.; Tyndall, A.; Walker, U.A.; Kay, J.; Søndergaard, Klaus; Carreira, P.E.; Morgiel, E.; Deuschle, K.; Derk, C.T.; Widuchowska, M.


    Objective: To assess patients with SSc who present without circulating antinuclear antibodies (ANA) or Raynaud’s phenomenon (RP). Methods: 5390 patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials And Research (EUSTAR) database were screened for the...

  8. Soya protein antibodies in man: their occurrence and possible relevance in coeliac disease.

    Haeney, M. R.; Goodwin, B. J.; Barratt, M E; Mike, N.; Asquith, P.


    Circulating antibodies to soya-derived protein antigens have been measured in patients with duodenitis, Crohn's disease, ulcerative colitis and coeliac disease. Significantly raised antibody titres were found frequently in the coeliac group, particularly those patients showing a suboptimal response to a gluten-free diet, but rarely in subjects with other gastrointestinal diseases. Antisoya activity was not necessarily accompanied by antibodies to other common dietary antigens. We suggest that...

  9. Macrophages are critical effectors of antibody therapies for cancer.

    Weiskopf, Kipp; Weissman, Irving L


    Macrophages are innate immune cells that derive from circulating monocytes, reside in all tissues, and participate in many states of pathology. Macrophages play a dichotomous role in cancer, where they promote tumor growth but also serve as critical immune effectors of therapeutic antibodies. Macrophages express all classes of Fcγ receptors, and they have immense potential to destroy tumors via the process of antibody-dependent phagocytosis. A number of studies have demonstrated that macrophage phagocytosis is a major mechanism of action of many antibodies approved to treat cancer. Consequently, a number of approaches to augment macrophage responses to therapeutic antibodies are under investigation, including the exploration of new targets and development of antibodies with enhanced functions. For example, the interaction of CD47 with signal-regulatory protein α (SIRPα) serves as a myeloid-specific immune checkpoint that limits the response of macrophages to antibody therapies, and CD47-blocking agents overcome this barrier to augment phagocytosis. The response of macrophages to antibody therapies can also be enhanced with engineered Fc variants, bispecific antibodies, or antibody-drug conjugates. Macrophages have demonstrated success as effectors of cancer immunotherapy, and further investigation will unlock their full potential for the benefit of patients. PMID:25667985

  10. Pre-existing Antibody: Biotherapeutic Modality-Based Review.

    Gorovits, Boris; Clements-Egan, Adrienne; Birchler, Mary; Liang, Meina; Myler, Heather; Peng, Kun; Purushothama, Shobha; Rajadhyaksha, Manoj; Salazar-Fontana, Laura; Sung, Crystal; Xue, Li


    Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed. PMID:26821802

  11. Resolvability in Circulant Graphs

    Muhammad SALMAN; Imran JAVAID; Muhammad Anwar CHAUDHRY


    A set W of the vertices of a connected graph G is called a resolving set for G if for every two distinct vertices u,v ∈ V(G) there is a vertex w ∈ W such that d(u,w) ≠ d(v,w).A resolving set of minimum cardinality is called a metric basis for G and the number of vertices in a metric basis is called the metric dimension of G,denoted by dim(G).For a vertex u of G and a subset S of V(G),the distance between u and S is the number mins∈s d(u,s).A k-partition H ={S1,S2,...,Sk} of V(G) is called a resolving partition if for every two distinct vertices u,v ∈ V(G) there is a set Si in Π such that d(u,Si) ≠ d(v,Si).The minimum k for which there is a resolving k-partition of V(G) is called the partition dimension of G,denoted by pd(G).The circulant graph is a graph with vertex set Zn,an additive group ofintegers modulo n,and two vertices labeled i and j adjacent if and only if i - j (mod n) ∈ C,where C C Zn has the property that C =-C and 0(∈) C.The circulant graph is denoted by Xn,△ where A =|C|.In this paper,we study the metric dimension of a family of circulant graphs Xn,3 with connection set C ={1,-n/2,n - 1} and prove that dim(Xn,3) is independent of choice of n by showing that 3 for all n =0 (mod 4),dim(X,n,3) ={ 4 for all n =2 (mod 4).We also study the partition dimension of a family of circulant graphs Xn,4 with connection set C ={±1,±2} and prove that pd(Xn,4) is independent of choice of n and show that pd(X5,4) =5 and 3 forall odd n≥9,pd(Xn,4) ={ 4 for all even n ≥ 6 and n =7.

  12. Engineering antibody therapeutics.

    Chiu, Mark L; Gilliland, Gary L


    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  13. Circulation of Stars

    Boitani, P.


    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  14. Antibody and B cell responses to Plasmodium sporozoites

    Johanna N Dups


    Full Text Available Antibodies are capable of blocking infection of the liver by Plasmodium sporozoites. Accordingly the induction of anti-sporozoite antibodies is a major aim of various vaccine approaches to malaria. In recent years our knowledge of the specificity and quantities of antibodies required for protection has been greatly expanded by clinical trials of various whole sporozoite and subunit vaccines. Moreover, the development of humanized mouse models and transgenic parasites have also aided our ability to assess the specificity of antibodies and their ability to block infection. Nonetheless, considerable gaps remain in our knowledge - in particular in understanding what antigens are recognized by infection blocking antibodies and in knowing how we can induce robust, long-lived antibody responses. Maintaining high levels of circulating antibodies is likely to be of primary importance, as antibodies must block infection in the short time it takes for sporozoites to reach the liver from the skin. It is clear that a better understanding of the development of protective B cell-mediated immunity will aid the development and refinement of malaria vaccines.


    Gallardo-Romero, Nadia F; Aréchiga-Ceballos, Nidia; Emerson, Ginny L; Martínez-Martínez, Flor O; Doty, Jeffrey B; Nakazawa, Yoshinori J; Rendón-Franco, Emilio; Muñoz-García, Claudia I; Villanueva-García, Claudia; Ramírez-Cid, Citlali; Gama-Campillo, Lilia M; Gual-Sill, Fernando; Aguilar-Setién, Álvaro; Carroll, Darin S


    Limited serosurveillance studies suggested that orthopoxviruses (OPXV) are widespread in the US (e.g., Raccoonpox virus, Skunkpox virus, Volepox virus) and Brazil (Vaccinia virus); however, their animal reservoir(s) remain unconfirmed. Mexican mammal diversity includes several species related to those in which evidence for OPXV infections has been found (Oryzomys, Peromyscus, Microtus, and Procyonidae). The presence of these groups of mammals in Mexico and the evidence of their possible involvement in the maintenance of OPXV in nature suggest the same or similar OPXV are circulating in Mexico. We tested 201 sera from 129 procyonids via modified enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) to estimate OPXV antibody prevalence in these animals. We detected a prevalence of 16.67% in Nasua narica (white-nosed coati), 35% in Procyon lotor (raccoon), and 30.4% in Bassariscus astutus (ring-tailed cat) when tested by either ELISA or WB. Western blot results presented protein bands consistent with the size of some OPXV immunodominant bands (14, 18, 32, 36, and 62 kDa). These results support the hypothesis that OPXV circulate in at least three genera of Procyonidae in Central and Southeast Mexico. PMID:27224209

  16. Bone marrow dosimetry for monoclonal antibody therapy

    Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

  17. Ocean General Circulation Models

    Yoon, Jin-Ho; Ma, Po-Lun


    1. Definition of Subject The purpose of this text is to provide an introduction to aspects of oceanic general circulation models (OGCMs), an important component of Climate System or Earth System Model (ESM). The role of the ocean in ESMs is described in Chapter XX (EDITOR: PLEASE FIND THE COUPLED CLIMATE or EARTH SYSTEM MODELING CHAPTERS). The emerging need for understanding the Earth’s climate system and especially projecting its future evolution has encouraged scientists to explore the dynamical, physical, and biogeochemical processes in the ocean. Understanding the role of these processes in the climate system is an interesting and challenging scientific subject. For example, a research question how much extra heat or CO2 generated by anthropogenic activities can be stored in the deep ocean is not only scientifically interesting but also important in projecting future climate of the earth. Thus, OGCMs have been developed and applied to investigate the various oceanic processes and their role in the climate system.

  18. Trypanosoma cruzi: circulating antigens

    V. Bongertz


    Full Text Available Circulating antigens were detected in sera of mice experimentally infected with a high close of Trypanosoma cruzi by reaction with sera from chronically infected mice. The immunodiffusion reaction between homologous acute and chronic sera produced four precipitation lines. By reaction with chronic mouse serum, circulating antingens were detected in sera from heavily infected hamsters, dogs, rabbits and in sera from chagasic patients. A reaction was also found in urine from acutely infected mice and dogs. Trypanosoma cruzi exoantigen was detected in trypanosome culture medium and in the supernatant of infected cell cultures. Attempts to isolate the antigens are described.Antígenos circulantes foram detectados em soros de camundongos infectados experimentalmente com elevadas doses de Trypanosoma cruzi pela reação com soros obtidos de camundongos em fase crônica de infecção. A reação de imunodifusão entre soros homólogos agudo e crônico produziu quatro linhas de precipitação. Por reação com soro crônico de camundongo antígenos circulantes foram detectados em soros de crícetos, cães e coelhos infectados com doses elevadas de Trypanosoma cruzi e em soros de pacientes chagásicos. Uma reação foi também observada com urina de camundongos e cães infectados de forma aguda. Exoantígeno de Trypanosoma cruzi foi detectado em meio de cultura de tripanosomas e em sobrenadantes de culturas de células infectadas. Tentativas de isolamento dos antigenos são descritas.

  19. Affinity purification of antibodies

    Antibodies are provided in a variety of formats that includes antiserum, hybridoma culture supernatant or ascites. They can all be used successfully in crude form for the detection of target antigens by immunoassay. However, it is advantageous to use purified antibody in defined quantity to facil...

  20. Therapeutic Recombinant Monoclonal Antibodies

    Bakhtiar, Ray


    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…

  1. Production Of Human Antibodies

    Sammons, David W.; Neil, Garry A.


    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  2. RBC Antibody Screen

    ... the baby is Rh-positive and the mother's antibody status is negative for anti-D, the mother is given additional RhIG. This test also may be used to help diagnose autoimmune-related hemolytic anemia ... when a person produces antibodies against his or her own RBC antigens. This ...

  3. Antibody affinity maturation

    Skjødt, Mette Louise

    Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...

  4. Selection of Recombinant Human Antibodies.

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André


    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies. PMID:27236551

  5. TROPICAL METEOROLOGY & Climate: Hadley Circulation

    Lu, Jian; Vecchi, Gabriel A.


    The Hadley circulation, a prominent circulation feature characterized by rising air near the Equator and sinking air in the subtropics, defines the position of dry subtropical areas and is a fundamental regulator of the earth’s energy and momentum budgets. The character of the Hadley circulation, and its related precipitation regimes, exhibits variation and change in response to both climate variability and radiative forcing changes. The strength and position of the Hadley circulation change from year to year paced by El Niño and La Niña events. Over the last few decades of the twentieth century, the Hadley cell has expanded poleward in both hemispheres, with changes in atmospheric composition (including stratospheric ozone depletion and greenhouse gas increases) thought to have contributed to its expansion. This article introduces the basic phenomenology and driving mechanism of the Hadley circulation and discusses its variations under both natural and anthropogenic climate forcings.

  6. Sino-Danish Brain Circulation

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe


    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...

  7. Antibody discovery: sourcing of monoclonal antibody variable domains.

    Strohl, William R


    Historically, antibody variable domains for therapeutic antibodies have been sourced primarily from the mouse IgG repertoire, and typically either chimerized or humanized. More recently, human antibodies from transgenic mice producing human IgG, phage display libraries, and directly from human B lymphocytes have been used more broadly as sources of antibody variable domains for therapeutic antibodies. Of the total 36 antibodies approved by major maket regulatory agencies, the variable domain sequences of 26 originate from the mouse. Of these, four are marketed as murine antibodies (of which one is a mouse-rat hybrid IgG antibody), six are mouse-human chimeric antibodies, and 16 are humanized. Ten marketed antibodies have originated from human antibody genes, three isolated from phage libraries of human antibody genes and seven from transgenic mice producing human antibodies. Five antibodies currently in clinical trials have been sourced from camelids, as well as two from non-human primates, one from rat, and one from rabbit. Additional sources of antibody variable domains that may soon find their way into the clinic are potential antibodies from sharks and chickens. Finally, the various methods for retrieval of antibodies from humans, mouse and other sources, including various display technologies and amplification directly from B cells, are described. PMID:24168292

  8. Natural Circulation with Boiling

    A number of parameters with dominant influence on the power level at hydrodynamic instability in natural circulation, two-phase flow, have been studied experimentally. The geometrical dependent quantities were: the system driving head, the boiling channel and riser dimensions, the single-phase as well as the two phase flow restrictions. The parameters influencing the liquid properties were the system pressure and the test section inlet subcooling. The threshold of instability was determined by plotting the noise characteristics in the mass flow records against power. The flow responses to artificially obtained power disturbances at instability conditions were also measured in order to study the nature of hydrodynamic instability. The results presented give a review over relatively wide ranges of the main parameters, mainly concerning the coolant performance in both single and parallel boiling channel flow. With regard to the power limits the experimental results verified that the single boiling channel performance was intimately related to that of the parallel channels. In the latter case the additional inter-channel factors with attenuating effects were studied. Some optimum values of the parameters were observed

  9. Targeting FcRn for the modulation of antibody dynamics.

    Ward, E Sally; Devanaboyina, Siva Charan; Ober, Raimund J


    The MHC class I-related receptor, FcRn, is a multitasking protein that transports its IgG ligand within and across cells of diverse origins. The role of this receptor as a global regulator of IgG homeostasis and transport, combined with knowledge of the molecular details of FcRn-IgG interactions, has led to opportunities to modulate the in vivo dynamics of antibodies and their antigens through protein engineering. Consequently, the generation of half-life extended antibodies has shown a rapid expansion over the past decade. Further, FcRn itself can be targeted by inhibitors to induce decreased levels of circulating IgGs, which could have applications in multiple clinical settings. The engineering of antibody-antigen interactions to reduce antibody-mediated buffering of soluble ligand has also developed into an active area of investigation, leading to novel antibody platforms designed to result in more effective antigen clearance. Similarly, the target-mediated elimination of antibodies by internalizing, membrane bound antigens (receptors) can be decreased using novel engineering approaches. These strategies, combined with subcellular trafficking analyses of antibody/antigen/FcRn behavior in cells to predict in vivo behavior, have considerable promise for the production of next generation therapeutics and diagnostics. PMID:25766596

  10. Radiolabelled antibodies in imaging

    Recent technological advances make it possible to produce pure (monoclonal) antibodies in unlimited quantities without the need for continuous immunization of animals and to label these antibodies with a variety of radionuclides which can be traced by single-photon computed tomography. An outline review of the state of the art is presented, with particular reference to the imaging of myocardial infarcts and to tumour imaging studies using labelled monoclonal antibodies (sup(99m)Tc and 125I). Lengthy bibliography. (U.K.)

  11. Naturally occurring autologous anti-idiotypic antibodies. Participation in immune complex formation in selective IgA deficiency


    50% of individuals of selective IgA deficiency have high serum titers of antibody to bovine proteins, and high levels of circulating immune complexes that contain bovine antigens. Because in animal studies, immunization with antigen-antibody complexes is a very effective means of producing anti-idiotypic antibodies, we sought such autoantibodies in two sera known to have large amounts of anticasein. After IgG isolation and two-stage affinity chromatography, IgG-like material (molecular weight...

  12. Prevalence of phocine distemper virus specific antibodies: bracing for the next seal epizootic in north-western Europe

    Bodewes, Rogier; Morick, Danny; van de Bildt, Marco WG; Osinga, Nynke; Rubio García, Ana; Sánchez Contreras, Guillermo J; Smits, Saskia L.; Reperant, Leslie AP; Kuiken, Thijs; Osterhaus, Albert DME


    In 1988 and 2002, two major phocine distemper virus (PDV) outbreaks occurred in harbour seals (Phoca vitulina) in north-western European coastal waters, causing the death of tens of thousands seals. Here we investigated whether PDV is still circulating among seals of the Dutch coastal waters and whether seals have protective serum-antibodies against PDV. Therefore seal serum samples, collected from 2002 to 2012, were tested for the presence of PDV-neutralizing antibodies. Antibodies were dete...

  13. Ratio of Circulating IFNγ+ “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi


    Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ+Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ+Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146

  14. Anti-sulfotyrosine antibodies

    Bertozzi, Carolyn R.; Kehoe, John; Bradbury, Andrew M.


    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  15. HIV Antibody Test

    ... be limited. Home Visit Global Sites Search Help? HIV Antibody and HIV Antigen (p24) Share this page: Was this page helpful? Also known as: HIV Screening Tests; AIDS Test; AIDS Screen; HIV Serology; ...

  16. Antinuclear antibody panel

    ... blood may be due to: Chronic liver disease Collagen vascular disease Drug-induced lupus erythematosus Myositis (inflammatory muscle disease) ... Saunders; 2011:chap 51. Read More Antibody Arthritis Collagen vascular disease Drug-induced lupus erythematosus Liver disease Scleroderma Systemic ...




    Full Text Available The article considers the use of monoclonal antibodies in immunotherapy and immunodiagnostics of oncological diseases and their production using hybridoma technolody with flow diagram and technological scheme of manufacturing process




    The article considers the use of monoclonal antibodies in immunotherapy and immunodiagnostics of oncological diseases and their production using hybridoma technolody with flow diagram and technological scheme of manufacturing process

  19. Expression of Recombinant Antibodies

    Frenzel, André; Hust, Michael; Schirrmann, Thomas


    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transg...

  20. The circulation physiology of agroecosystems

    Cao Zhiping; Richard Dawson


    This paper represents an effort to enlarge the understanding of the biophysical foundation of agroecosystems by using an analogy with the circulation of the blood in the human body. The circulation function in the human body can be represented as arterial pressure. The factors affecting arterial pressure in the human body have direct counterparts in the cultivation-husbandry system. The relationship between circulation pressure and the factors affecting that pressure in the cultivation-husbandry system are similar to the relationship between the arterial pressure and factors affecting arterial pressure in the human body. Furthermore, circulation resistance in the cultivation-husbandry system can be shown to be analogous to the calculation of peripheral resistance in the human body by Poiseuille's formula.

  1. Influenza-Specific Antibody-Dependent Phagocytosis

    Ana-Sosa-Batiz, Fernanda; Vanderven, Hillary; Jegaskanda, Sinthujan; Johnston, Angus; Rockman, Steven; Laurie, Karen; Barr, Ian; Reading, Patrick; Lichtfuss, Marit; Kent, Stephen J.


    Background Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized. Methods We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques. Results We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity in vitro. Conclusion We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection in vitro. Repeated exposure of humans to multiple IAV infections likely leads to the development of ADP that is cross-reactive to strains not previously encountered. Further analyses of the protective capacity of broadly reactive influenza-specific ADP is warranted. PMID:27124730

  2. Tracking hantavirus nucleocapsid protein using intracellular antibodies

    Liang Mifang


    Full Text Available Abstract Background Hantavirus nucleocapsid (N protein is a multifunctional viral macromolecule involved in multiple stages of the viral replication cycle. The intracellular trafficking of N protein during virus assembly remains unclear. Methods We used N protein-specific intracellular expressed antibodies to track the localization and distribution of Hantaan virus and Seoul virus N protein. The N protein-specific antibody single-chain variable antibody fragments (scFvs, which bind an N-terminal linear epitope (L13F3 and C-terminal conformational domain (H34, were intracellularly expressed in the endoplasmic reticulum (ER by fusion of the SEKDEL retention signal peptide at the carboxyl terminus, and in the cytoplasm (Cyto by deletion of the ER membrane target signal peptide. Stable Vero-E6 cell lines expressing intracellular scFvs were either infected with hantavirus or transfected with an N protein expression plasmid; virus replication and N protein intracellular localization were determined. Result N protein co-localized with scFvs in the ER and cytoplasm with or without viral membrane glycoproteins. Hantavirus replication was inhibited in both the scFvs-ER- and scFvs-Cyto-expressing stable cell lines. Conclusion N protein may be expressed in the ER retention signal peptide of KDEL circulating region (ER/cis-Golgi without the assistance of G protein, and so expression of N protein in both the cytoplasm and within the ER/cis-Golgi plays an important role in virus replication.

  3. Atmospheric Circulation of Terrestrial Exoplanets

    Showman, Adam P.; Wordsworth, Robin D.; Merlis, Timothy M.; Kaspi, Yohai


    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical a...

  4. Natural antibodies sustain differentiation and maturation of human dendritic cells

    Bayry, Jagadeesh; Lacroix-Desmazes, Sébastien; Donkova-Petrini, Vladimira; Carbonneil, Cédric; Misra, Namita; Lepelletier, Yves; Delignat, Sandrine; Varambally, Sooryanarayana; Oksenhendler, Eric; Lévy, Yves; Debré, Marianne; Kazatchkine, Michel D.; Hermine, Olivier; Kaveri, Srini V.


    The differentiation and maturation of dendritic cells (DCs) is governed by various signals in the microenvironment. Monocytes and DCs circulate in peripheral blood, which contains high levels of natural antibodies (NAbs). NAbs are germ-line-encoded and occur in the absence of deliberate immunization or microbial aggression. To assess the importance of NAbs in the milieu on DC development, we examined the status of DCs in patients with X-linked agammaglobulinemia, a disease characterized by pa...

  5. Clearance of injected radioactively labelled antibodies to tumour products by liposome-bound second antibodies

    Liposomes containing anti-goat immunoglobulin were injected 24 h after administration of 125I-labelled goat antibody against the carcinoembryonic antigen (anti-CEA) to groups of nude mice bearing human tumour xenografts, and normal mice. Controls in each group received radioactively labelled anti-CEA only. In liposome-treated mice, blood 125I levels were lower than those of controls 30 min to 24 h after liposome administration, with corresponding accumulation of 125I activity in the liver and spleen for the first 2 h after liposome injection. [14C]Cholesterol or sup(99m)Tc labels in the bilayer were eliminated rapidly from the blood, with uptake in the liver and spleen. In xenograft-bearing mice, 125I activity detected in the tumours up to 6 h after liposome injection was identical to that detected in the tumours of controls. However, 24 h after liposome injection a reduction in the tumour concentration of 125I-labelled anti-CEA was obtained, but the tumour/blood radioactivity was still increased. In two mice given 27 μmol lipid, the blood radioactivity count after 24 h was only 5% of that in the controls. In rabbits, 2 h after administration of liposomes containing anti-goat second antibody, the circulating 125I activity had dropped by 28-40%. The results suggest that administration of liposome-entrapped second antibody approximately 2 h prior to external scintigraphy may clear circulating radioactively labelled primary antibody by up to 50%. (Auth.)

  6. The Clinical Potential of Circulating Tumor Cells; The Need to Incorporate a Modern “Immunological Cocktail” in the Assay

    Jonathan W. Uhr


    Full Text Available The accepted clinical assay, CellSearch®, and lab-on-a-chip tests for capturing circulating tumor cells are antibody-mediated. Attempts to improve their sensitivity have relied upon physical changes in the instruments. There have been no significant advances in improving the antibody-mediated portion of the capture. Modern immunologic engineering offers major possibilities for improving the sensitivity and other features of the assay. These include obtaining univalent antibody fragments such as scFvs with picomolar binding affinity and sufficient specificity; altering them to enhance their range of potential contact with target antigens; using antibodies directed against different epitopes on epithelial, mesenchymal or organ-specific cell surface markers to allow simultaneous binding and investigating non-antibody binding molecules as substitutes for antibody. These maneuvers could markedly improve the ability of current assays to improve patient care and might result in an acceptable test for detecting cancer earlier in high risk patients.

  7. The Clinical Potential of Circulating Tumor Cells; The Need to Incorporate a Modern “Immunological Cocktail” in the Assay

    The accepted clinical assay, CellSearch®, and lab-on-a-chip tests for capturing circulating tumor cells are antibody-mediated. Attempts to improve their sensitivity have relied upon physical changes in the instruments. There have been no significant advances in improving the antibody-mediated portion of the capture. Modern immunologic engineering offers major possibilities for improving the sensitivity and other features of the assay. These include obtaining univalent antibody fragments such as scFvs with picomolar binding affinity and sufficient specificity; altering them to enhance their range of potential contact with target antigens; using antibodies directed against different epitopes on epithelial, mesenchymal or organ-specific cell surface markers to allow simultaneous binding and investigating non-antibody binding molecules as substitutes for antibody. These maneuvers could markedly improve the ability of current assays to improve patient care and might result in an acceptable test for detecting cancer earlier in high risk patients

  8. Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

    Viana, H.; F. Nolasco; Santos, MC; Carvalho, F.; Galvão, MJ; Santos, AR; Bordalo, J; Ribeiro Santos, J


    BACKGROUND: Prospective testing for posttransplant circulating anti-HLA antibodies seems to be a critical noninvasive tool, but confirmatory data are lacking. MATERIALS AND METHODS: Over the last 3 years, peritubular capillary (PTC) C4d deposition was prospectively sought by an immunofluorescence technique applied to frozen tissue in biopsies obtained for allograft dysfunction. Screening for circulating anti-HLA class I/II alloantibodies (AlloAb) by the flow cytometric test was performed ...

  9. Tamm-Horsfall protein antibody in patients with end-stage kidney disease.

    Work, J; Andriole, V T


    Circulating antibody to Tamm-Horstall protein (THP) was measured using a radioimmunoassay in forty-five patients on maintenance hemodialysis and compared to levels of antibody titers measured in sera from ten healthy controls. The etiology of the end-stage kidney disease in the patient population was polycystic kidney disease in thirteen, glomerulonephritis in fourteen, diabetic nephropathy in nine, interstial nephritis and chronic pyelonephritis in three each, multiple myeloma in two, and ur...

  10. Anti-thyroid peroxidase antibodies: Its effect on thyroid gland and breast tissue

    Sabitha Kandi; Pragna Rao


    Thyroid peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormone. TPO is involved in thyroid hormone synthesis (organification and coupling reactions). TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti-TPO auto antibodies are very important to diagnose autoimmune thyroid diseases and also in estimating its clinical course. Autoimmune thyroid disease is detected mostly by measuring circulating antibodies to thyroglobulin which is uncommon measurement o...

  11. Bipolar disorder and antithyroid antibodies: review and case series.

    Bocchetta, Alberto; Traccis, Francesco; Mosca, Enrica; Serra, Alessandra; Tamburini, Giorgio; Loviselli, Andrea


    Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms. PMID:26869176

  12. Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1-Infected Individuals from Guinea-Bissau and Denmark.

    Borggren, Marie; Jensen, Sanne Skov; Heyndrickx, Leo; Palm, Angelica A; Gerstoft, Jan; Kronborg, Gitte; Hønge, Bo Langhoff; Jespersen, Sanne; da Silva, Zacarias José; Karlsson, Ingrid; Fomsgaard, Anders


    The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory activity than that from Guinea-Bissau individuals against both local and nonlocal virus strains. Interestingly, an opposite pattern was observed with ADCC activity, where Guinea-Bissau individual plasma demonstrated higher activity than Danish plasma and was specifically against the local circulating subtype. Thus, on basis of samples from these two cohorts, no local-specific neutralizing activity was detected, but a local ADCC response was identified in the Guinea-Bissau samples, suggesting potential use of regional immunogens for an ADCC-inducing vaccine. PMID:26621287

  13. Circulation of antibodies against yellow fever virus in a simian population in the area of Porto Primavera Hydroelectric Plant, São Paulo, Brazil Circulação de anticorpos contra o vírus amarílico em população simiana da região da usina hidrelétrica de Porto Primavera, São Paulo, Brasil

    Maura Antonia Lima


    Full Text Available Yellow fever (YF is an acute viral infectious disease transmitted by mosquitoes which occurs in two distinct epidemiological cycles: sylvatic and urban. In the sylvatic cycle, the virus is maintained by monkey's infection and transovarian transmission in vectors. Surveillance of non-human primates is required for the detection of viral circulation during epizootics, and for the identification of unaffected or transition areas. An ELISA (enzyme-linked immunosorbent assay was standardized for estimation of the prevalence of IgG antibodies against yellow fever virus in monkey sera (Alouatta caraya from the reservoir area of Porto Primavera Hydroelectric Plant, in the state of São Paulo, Brazil. A total of 570 monkey sera samples were tested and none was reactive to antibodies against yellow fever virus. The results corroborate the epidemiology of yellow fever in the area. Even though it is considered a transition area, there were no reports to date of epizootics or yellow fever outbreaks in humans. Also, entomological investigations did not detect the presence of vectors of this arbovirus infection. ELISA proved to be fast, sensitive, an adequate assay, and an instrument for active search in the epidemiological surveillance of yellow fever allowing the implementation of prevention actions, even before the occurrence of epizootics.A febre amarela (FA é doença infecciosa aguda de origem viral transmitida por mosquitos. No ciclo silvestre, o vírus é mantido por meio da infecção de macacos e da transmissão transovariana nos vetores. A vigilância sobre populações de primatas não humanos torna-se necessária para detectar a circulação viral, quando ainda está restrito a epizootias, e para determinar sua presença em regiões indenes ou de transição para a doença. Padronizou-se a técnica ELISA (Enzyme Linked Immunosorbent Assay para determinar a prevalência de anticorpos da classe IgG contra o vírus da FA em soros de bugios (Alouatta

  14. PCSK9 Antibodies for the Treatment of Hypercholesterolemia

    Ioanna Gouni-Berthold


    Full Text Available The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9 binds to the low-density lipoprotein (LDL receptor (LDLR and directs it to lysosomes for intracellular degradation. This results in decreased numbers of LDLR available on the hepatic cell surface to bind LDL particles and remove them from the circulation and therefore to a subsequent increase in circulating LDL-cholesterol (LDL-C plasma levels. Since 2003, when the role of PCSK9 in LDL-C metabolism was discovered, there have been major efforts to develop efficient and safe methods to inhibit it. Amongst those, monoclonal antibodies against PCSK9 are the furthest in development, with multiple phase 3 trials already published and with cardiovascular endpoint trials currently underway. Two fully human monoclonal antibodies, evolocumab (AMG 145 and alirocumab (REGN727/SAR236553, have been extensively studied in a wide range of subjects, such as those with statin intolerance, as an add-on to statin therapy, as a monotherapy and in patients with familial hypercholesterolemia. PCSK9 antibodies result in a consistent and robust decrease in LDL-C plasma levels ranging from 40% to 70%, either on top of statins or as a monotherapy. If the safety data from the on-going phase 3 trials remain as reassuring as the data available till now, PCSK9 antibodies will offer a novel, powerful therapeutic option to decrease LDL-C plasma levels and, hopefully, cardiovascular risk.

  15. Epsilon haemoglobin specific antibodies with applications in noninvasive prenatal diagnosis

    Sørensen, Morten Draeby; Gonzalez Dosal, Regina; Jensen, Kim Bak;


    Invasive procedures for prenatal diagnosis are associated with increased risk of abortion; thus, development of noninvasive procedures would be beneficial. Based on the observation that embryonic nucleated red blood cell (NRBC) crosses the placenta and enters the circulation of pregnant women, the...... ability to identify such cell would allow development of such procedures. Identification of NRBCs in blood samples would be possible provided that specific antibodies are available. Here we have isolated recombinant antibodies using phage display. From the panel of antibody fragments specifically...... recognising epsilon-Hb, one was chosen for further characterization, DAb1. DAb1 binds to epsilon-Hb both in Western blots and immunocytochemistry. Several epsilon-Hb positive cells were detected in a blood sample taken as postchorionic villus sampling (CVS). To evaluate the sensitivity of the method, K562...

  16. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    Yao, Fengchao


    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model\\'s winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow. Key Points Sinking occurs in a narrow boundary layer along the eastern boundary Surface western boundary current switches into an eastern boundary current Water exchange in the Strait of Bab el Mandeb is not hydraulically controlled © 2014. American Geophysical Union. All Rights Reserved.

  17. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

    Zhaolin Jiang


    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  18. Circulating Fibronectin Controls Tumor Growth

    Anja von Au


    Full Text Available Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. The relative contribution of local and circulating fibronectin to blood vessel formation in vivo remains unknown despite evidence for unexpected roles of circulating fibronectin in various diseases. Using transgenic mouse models, we established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation. This effect is more relevant than that of fibronectin produced by endothelial cells and pericytes, which only exert a small additive effect on vessel maturation. Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. Consistent with these results, examination of three separate arrays from patients with breast and prostate cancers revealed that a high staining intensity for fibronectin in tumors is associated with increased mortality. These results establish that circulating fibronectin modulates blood vessel formation and tumor growth by modifying the amount of and the response to VEGF. Furthermore, determination of the fibronectin content can serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.

  19. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Gascoyne, Peter R. C., E-mail: [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Shim, Sangjo [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, C0800, Austin, TX 78712 (United States); Present address: Micro & Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, 208 North Wright Street, Urbana, IL 61801 (United States)


    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  20. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies

  1. Isolation of Circulating Tumor Cells by Dielectrophoresis

    Peter R. C. Gascoyne


    Full Text Available Dielectrophoresis (DEP is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a the principles of DEP; (b the biological basis for the dielectric differences between CTCs and blood cells; (c why such differences are expected to be present for all types of tumors; and (d instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  2. Prediction of antibody persistency from antibody titres to natalizumab

    Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn; Sørensen, Per S


    In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

  3. Atmospheric Circulation of Terrestrial Exoplanets

    Showman, Adam P; Merlis, Timothy M; Kaspi, Yohai


    The investigation of planets around other stars began with the study of gas giants, but is now extending to the discovery and characterization of super-Earths and terrestrial planets. Motivated by this observational tide, we survey the basic dynamical principles governing the atmospheric circulation of terrestrial exoplanets, and discuss the interaction of their circulation with the hydrological cycle and global-scale climate feedbacks. Terrestrial exoplanets occupy a wide range of physical and dynamical conditions, only a small fraction of which have yet been explored in detail. Our approach is to lay out the fundamental dynamical principles governing the atmospheric circulation on terrestrial planets--broadly defined--and show how they can provide a foundation for understanding the atmospheric behavior of these worlds. We first survey basic atmospheric dynamics, including the role of geostrophy, baroclinic instabilities, and jets in the strongly rotating regime (the "extratropics") and the role of the Hadle...

  4. Prediction of Antibody Epitopes

    Nielsen, Morten; Marcatili, Paolo


    self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  5. Monoclonal antibodies in myeloma

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


    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...

  6. Red Blood Cell Antibody Identification

    ... limited. Home Visit Global Sites Search Help? RBC Antibody Identification Share this page: Was this page helpful? Also known as: Alloantibody Identification; Antibody ID, RBC; RBC Ab ID Formal name: Red ...

  7. Anti-insulin antibody test

    Insulin antibodies - serum; Insulin Ab test ... Normally, there are no antibodies against insulin in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or ...

  8. The Art of Making Antibodies.

    Headon, Denis R.


    Provides background information for teachers on the nature and production of antibodies. Points out that the production of monoclonal antibodies blends the malignant with the beneficial to create a medical tool of exciting potential. (JN)

  9. Lupus anticoagulants and antiphospholipid antibodies

    ... this page: // Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  10. Porcine humoral immune responses to multiple injections of murine monoclonal antibodies

    Lohse, Louise; Nielsen, Jens; Kamstrup, Søren; Oleksiewicz, M.B.; Eriksen, L.

    cognate antigen in the pigs were used. Enzyme-linked immunosorbent assays (ELISA) were used to quantitate the circulating m-mAbs, as well as the induced pig anti-mouse antibodies (PAMA), in serum samples from m-mAb-treated pigs. As expected, we generally saw vigorous PAMA responses within 10 days aft er......In humans and cattle, multiple injections of murine monoclonal antibodies (m-mAbs) induce anti-mouse antibody responses. The objectives of the present. study were to investigate whether a similar response could be seen when pigs were subjected to m-mAb therapy, and to study the kinetics of such a...

  11. A novel antibody discovery platform identifies anti-influenza A broadly neutralizing antibodies from human memory B cells.

    Xiao, Xiaodong; Chen, Yan; Varkey, Reena; Kallewaard, Nicole; Koksal, Adem C; Zhu, Qing; Wu, Herren; Chowdhury, Partha S; Dall'Acqua, William F


    Monoclonal antibody isolation directly from circulating human B cells is a powerful tool to delineate humoral responses to pathological conditions and discover antibody therapeutics. We have developed a platform aimed at improving the efficiencies of B cell selection and V gene recovery. Here, memory B cells are activated and amplified using Epstein-Barr virus infection, co-cultured with CHO-muCD40L cells, and then assessed by functional screenings. An in vitro transcription and translation (IVTT) approach was used to analyze variable (V) genes recovered from each B cell sample and identify the relevant heavy/light chain pair(s). We achieved efficient amplification and activation of memory B cells, and eliminated the need to: 1) seed B cells at clonal level (≤1 cell/well) or perform limited dilution cloning; 2) immortalize B cells; or 3) assemble V genes into an IgG expression vector to confirm the relevant heavy/light chain pairing. Cross-reactive antibodies targeting a conserved epitope on influenza A hemagglutinin were successfully isolated from a healthy donor. In-depth analysis of the isolated antibodies suggested their potential uses as anti-influenza A antibody therapeutics and uncovered a distinct affinity maturation pathway. Importantly, our results showed that cognate heavy/light chain pairings contributed to both the expression level and binding abilities of our newly isolated VH1-69 family, influenza A neutralizing antibodies, contrasting with previous observations that light chains do not significantly contribute to the function of this group of antibodies. Our results further suggest the potential use of the IVTT as a powerful antibody developability assessment tool. PMID:27049174

  12. Recombinant antibodies and tumor targeting

    Sheikholvaezin, Ali


    Different antibody derived constructs are rapidly advancing as putative tools for treatment of malignant diseases. Antibody engineering has added significant new technologies to modify size, affinities, solubility, stability and biodistribution properties for immunoconjugates. In the present thesis, the aim was to increase our knowledge on how new recombinant antibodies could be tailored to optimize localization to experimental tumors in mice. One hybridoma, producing the monoclonal antibody ...

  13. Antibody Engineering and Therapeutics Conference

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A.; Burton, Dennis R.; Adams, Gregory P; Weiner, Louis M.; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M


    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Bi...

  14. Radiolabeled antibodies as imaging agents

    The author gives a survey of the progress made on radioimmunodetection. Antibodies may now be more readily used in scintigraphy as a result of the development of labeling methods that apply more suitable radionuclides without significant loss of the antigen-binding activity. Antibodies to tumor-specific or tumor-associated antigens can now be produced in large quantities by monoclonal antibody technology

  15. A Study of Anti Beta-2 Glycoprotein I and Anti-Prothrombin Antibodies in Patients with Unexplained Recurrent Pregnancy Losses.

    Singh, Angad; Nangia, Anita; Sharma, Sunita; Puri, Manju


    To compare the levels of IgG and IgM anti beta-2 glycoprotein I antibodies and IgG and IgM anti prothrombin antibodies among women with unexplained recurrent pregnancy losses and women with at least 2 live issues. To compare the prevalence of newer anti beta-2 glycoprotein I & anti prothrombin antibodies with conventional Lupus anticoagulant & anticardiolipin antibodies. 50 women with recurrent pregnancy losses & 50 matched controls were evaluated for the presence of: Lupus anticoagulant-screened by LA sensitive aPTT& DRVV and confirmatory Staclot Assay. ELISA kits were used for detecting IgG & IgM anticardiolipin, anti beta-2 glycoprotein I & anti prothrombin antibodies. 11/50 (22 %) women in study group and none in control group had circulating antiphospholipid antibodies. 2 cases (4 %) had lupus anticoagulant. 1 case (2 %) had anticardiolipin antibody & 6 cases (12 %) were positive for anti beta-2 Glycoprotein I antibody (p value = 0.027). 3 cases (6 %) had anti prothrombin antibody. All were mutually exclusive except for one. Women with recurrent pregnancy losses should be tested for anti beta-2 Glycoprotein I antibodies & anti prothrombin antibodies in addition to conventional lupus anticoagulant and anticardiolipin antibodies. This approach can decrease the incidence of SNAP (seronegative antiphospholipid syndrome) cases while establishing the true prevalence of antiphospholipid syndrome. PMID:27065583

  16. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help.

    Iijima, Norifumi; Iwasaki, Akiko


    Circulating antibodies can access most tissues to mediate surveillance and elimination of invading pathogens. Immunoprivileged tissues such as the brain and the peripheral nervous system are shielded from plasma proteins by the blood-brain barrier and blood-nerve barrier, respectively. Yet, circulating antibodies must somehow gain access to these tissues to mediate their antimicrobial functions. Here we examine the mechanism by which antibodies gain access to neuronal tissues to control infection. Using a mouse model of genital herpes infection, we demonstrate that both antibodies and CD4 T cells are required to protect the host after immunization at a distal site. We show that memory CD4 T cells migrate to the dorsal root ganglia and spinal cord in response to infection with herpes simplex virus type 2. Once inside these neuronal tissues, CD4 T cells secrete interferon-γ and mediate local increase in vascular permeability, enabling antibody access for viral control. A similar requirement for CD4 T cells for antibody access to the brain is observed after intranasal challenge with vesicular stomatitis virus. Our results reveal a previously unappreciated role of CD4 T cells in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread. PMID:27225131

  17. VanderLaan Circulant Type Matrices

    Hongyan Pan


    Full Text Available Circulant matrices have become a satisfactory tools in control methods for modern complex systems. In the paper, VanderLaan circulant type matrices are presented, which include VanderLaan circulant, left circulant, and g-circulant matrices. The nonsingularity of these special matrices is discussed by the surprising properties of VanderLaan numbers. The exact determinants of VanderLaan circulant type matrices are given by structuring transformation matrices, determinants of well-known tridiagonal matrices, and tridiagonal-like matrices. The explicit inverse matrices of these special matrices are obtained by structuring transformation matrices, inverses of known tridiagonal matrices, and quasi-tridiagonal matrices. Three kinds of norms and lower bound for the spread of VanderLaan circulant and left circulant matrix are given separately. And we gain the spectral norm of VanderLaan g-circulant matrix.

  18. Conservation of Circulation in Magnetohydrodynamics

    Bekenstein, J D; Bekenstein, Jacob D.; Oron, Asaf


    We demonstrate, both at the Newtonian and (general) relativistic levels, theexistence of a generalization of Kelvin's circulation theorem (for pure fluids)which is applicable to perfect magnetohydrodynamics. The argument is based onthe least action principle for magnetohydrodynamic flow. Examples of the newconservation law are furnished. The new theorem should be helpful inidentifying new kinds of vortex phenomena distinct from magnetic ropes or fluidvortices.

  19. Neural Control of the Circulation

    Thomas, Gail D.


    The purpose of this brief review is to highlight key concepts about the neural control of the circulation that graduate and medical students should be expected to incorporate into their general knowledge of human physiology. The focus is largely on the sympathetic nerves, which have a dominant role in cardiovascular control due to their effects to…

  20. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying


    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed. PMID:25264572

  1. Apoptosis of circulating lymphocytes during pediatric cardiac surgery

    Bocsi, J.; Pipek, M.; Hambsch, J.; Schneider, P.; Tárnok, A.


    There is a constant need for clinical diagnostic systems that enable to predict disease course for preventative medicine. Apoptosis, programmed cell death, is the end point of the cell's response to different induction and leads to changes in the cell morphology that can be rapidly detected by optical systems. We tested whether apoptosis of T-cells in the peripheral blood is useful as predictor and compared different preparation and analytical techniques. Surgical trauma is associated with elevated apoptosis of circulating leukocytes. Increased apoptosis leads to partial removal of immune competent cells and could therefore in part be responsible for reduced immune defence. Cardiovascular surgery with but not without cardiopulmonary bypass (CPB) induces transient immunosuppression. Its effect on T-cell apoptosis has not been shown yet. Flow-cytometric data of blood samples from 107 children (age 3-16 yr.) who underwent cardiac surgery with (78) or without (29) CPB were analysed. Apoptotic T-lymphocytes were detected based on light scatter and surface antigen (CD45/CD3) expression (ClinExpImmunol2000;120:454). Results were compared to staining with CD3 antibodies alone and in the absence of antibodies. T-cell apoptosis rate was comparable when detected with CD45/CD3 or CD3 alone, however not in the absence of CD3. Patients with but not without CPB surgery had elevated lymphocyte apoptosis. T-cell apoptosis increased from 0.47% (baseline) to 0.97% (1 day postoperatively). In CPB patients with complication 1.10% significantly higher (ANOVA p=0.01) comparing to CPB patients without complications. Quantitation of circulating apoptotic cells based on light scatter seems an interesting new parameter for diagnosis. Increased apoptosis of circulating lymphocytes and neutrophils further contributes to the immune suppressive response to surgery with CPB. (Support: MP, Deutsche Herzstiftung, Frankfurt, Germany)

  2. Radiosensitivity of antibody responses and radioresistant secondary tetanus antitoxin responses

    Primary tetanus antitoxin responses were increasingly repressed in mice when gamma radiation doses of 100 to 400 rads were delivered by whole-body exposure prior to immunization with fluid tetanus toxoid (FTT). Nearly normal secondary antitoxin responses were obtained in mice exposed to 600 rads of gamma radiation 4 days after secondary antigenic stimulation with FTT. A rapid transition from radiosensitivity of the antibody-forming system on days 1 to 3 was followed by relative radioresistance on day 4 after the booster injection of toxoid. Studies on lymphoid cellular kinetics in popliteal lymph nodes after injection of 3H--thymidine (3H--TdR) and incorporation of 3H--L-histidine into circulating antitoxin were carried out. Analysis of tritium radioactivity in antigen--antibody precipitates of serums 2 hr after injection of the labeled amino acid revealed maximum incorporation into antibody around day 7 after the booster in nonirradiated controls and about day 12, i.e., 8 days after irradiation, in experimental mice. The shift from radiosensitivity to relative radioresistance was attributed to a marked peak of plasma-cell proliferation in the medulla of lymph nodes on day 3. Many medullary plasma cells survived and continued to proliferate after exposure to radiation. Germinal centers were destroyed by radiation within 1 day. Since antibody formation continued after exposure to radiation and after the loss of germinal centers, this supports the view that germinal-center cells were involved more in the generation of memory cells than in antibody synthesis

  3. Monoclonal antibodies to Pneumocystis carinii

    Kovacs, J A; Halpern, J L; Lundgren, B; Swan, J C; Parrillo, J E; Masur, H


    To increase understanding of the antigenic structure of Pneumocystis carinii, we developed monoclonal antibodies to rat and human P. carinii. The specificity of the antibodies was demonstrated by immunofluorescence and immunoblot studies. Only one of five monoclonal antibodies to rat P. carinii...... reacted with human P. carinii, and none of four monoclonal antibodies to human P. carinii reacted with rat P. carinii. Two antibodies to human P. carinii reacted by immunofluorescence with only one human P. carinii isolate. Immunoblot studies identified major antigens of rat P. carinii with molecular...

  4. [Antibody therapy for Alzheimer's disease].

    Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng


    In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially. PMID:22277519

  5. Tabhu: tools for antibody humanization

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna


    and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps......Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can...

  6. GAD65 antibodies among Greenland Inuit and its relation to glucose intolerance

    Pedersen, Michael Lynge; Bjerregaard, Peter; Jørgensen, Marit Eika


    fasting glycemia, (3) with impaired glucose tolerance and (4) with previously unknown diabetes based on oral glucose tolerance test and were enrolled in the study. Presence of circulating Glutamin-Acid-decarboxylase 65 antibodies were measured in all participants. A total of 484 persons were enrolled in...

  7. Antibodies to Infliximab and Adalimumab in Patients with Rheumatoid Arthritis in Clinical Remission

    Eng, Grith P; Bendtzen, Klaus; Bliddal, Henning;


    Objective. To investigate if antibodies towards biological TNF-α inhibitors (anti-TNFi Abs) are present in patients with rheumatoid arthritis (RA) in clinical remission and to relate any anti-TNFi Abs to circulating level of TNF-α inhibitor (TNFi). Methods. Patients with RA, treated with infliximab...

  8. Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection.

    Chan, Kuan Rong; Zhang, Summer Li-Xin; Tan, Hwee Cheng; Chan, Ying Kai; Chow, Angelia; Lim, Angeline Pei Chiew; Vasudevan, Subhash G; Hanson, Brendon J; Ooi, Eng Eong


    The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development. Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcγR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake. However, FcγR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcγRIIB, which is expressed at low levels but which inhibits FcγR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes. PMID:21746897

  9. Monoclonal antibody as radiopharmaceutical

    The purification of anti-CEA monoclonal antibody 4C11 belonging to IgG sub(2a) subclass from mouse ascitis, donated by Ludwig Institute, Brazil was developed. The fragmentation of purified IgG sub(2a) by pepsin digestion and analytical studies by polyacrilamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) were done as preliminary assessment for their specific application in immunoscintigraphy. (author)

  10. Anticardiolipin antibodies in leptospirosis.

    Rugman, F P; Pinn, G.; Palmer, M. F.; Waite, M.; Hay, C. R.


    The clinical course and serology of 16 cases of leptospirosis in an area with an unusually high endemic infection rate were studied to gain further insight into the pathology of the secondary immune phase that is typical of the disease. IgG anticardiolipin antibody concentrations were measured by immunoassay and found to be increased in eight serologically confirmed cases with severe complicated disease, compared with eight patients with relatively uncomplicated leptospirosis who had IgG anti...

  11. A monoclonal antibody against leptin.

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


    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. PMID:23098305

  12. Antiphospholipid Antibody and Antiphospholipid Syndrome



    @@ Antiphospholipid antibodies (APA) APA is a big category for all kinds of negative charge phospholipid or lecithin - a protein complex autoantibodies or the same antibody, through its recognition of antigen (target protein) different, and phospholipids or lecithin - protein complex combination of various rely on the interference Phospholipid clotting and anti-coagulation factor, and promote endothelial cells, platelets, complement activation and play a role. APA including lupus anticoagulant(LA) and anticardiolipin antibody (ACA), In addition, there are anti-β2 glycoprotein-I (β2-GPI) antibody, anti-prothrombin (a- PT) antibody, anti-lysophosphatidic acid antibody and anti-phosphatidylserine antibody, and so on. APA as the main target of phospholipid-binding protein, including β2-GPI, prothrombin, annexin, protein C (PC) and protein S (PS), plasminogen, and so on.

  13. Circulating Immune Complexes among Diabetic Children

    George Nicoloff


    Full Text Available Insulin dependent diabetes mellitus (IDDM is an autoimmune disease associated with the presence of different types of autoantibodies. The presence of these antibodies and the corresponding antigens in the circulation leads to the formation of circulating immune complexes (CIC. CIC are known to persist in the blood for long periods of time. Such CIC following deposition in the small blood vessels have the potential to lead to microangiopathy with debilitating clinical consequences. The aim of our pilot study was to investigate whether a correlation exists between CIC and the development of microvascular complications in diabetic children. Isolation of a new glycoprotein complement inhibition factor (CIF from the parasitic plant Cuscuta europea seed, which appears to bind specifically to complement component C3 has provided an unique tool for the measurement of immune complexes by means of ELISA-type techniques (CIF-ELISA. We studied the levels of CIC (IgG, IgM and IgA in 58 diabetic children (mean age 12.28±4.04 years, diabetes duration 5.3±3.7 years, 29 of them had vascular complications (group 1 and the other 29 were without vascular complications (group 2. As controls, we studied sera samples from 21 healthy children (mean age 13.54±4.03 years. Sera from the diabetic patients showed statistically significant higher levels of CIC IgG ( p=0.03 than sera from the control group. In sera from group 1 values of CIC IgG showed statistically significant higher levels than controls (0.720±0.31 vs. 0.46±0.045; p=0.011 Sera from 59% of the patients were positive for CIC IgG, 36% for CIC IgM and 9% for CIC IgA. Among 26 patients with microalbuminuria, sera from 17/26 (65% were positive for CIC IgG, 8/26 (31% for CIC IgM and 2/26 (8% for CIC IgA. CIC IgG correlated with HbA1c (r=0.51; p=0.005 and microalbuminuria (r=0.42, p=0.033. CIC IgA correlated with age (r=0.44, p=0.03. CIC IgM correlated with the duration of diabetes (r=0.63, p=0.02. These

  14. Comparative efficacy of antigen and antibody detection tests for human trichinellosis

    Sera collected from patients with suspected or confirmed exposure to Trichinella spiralis were tested for circulating parasite antigens and antiparasite antibodies. Using an immunoradiometric assay, excretory--secretory antigens from muscle-stage larvae of T. spiralis were detected in the sera of 47% of 62 patients with clinical trichinellosis and 13% of 39 patients without clinical signs but suspected of exposure to infected meat. In comparison, antibodies were detected using an indirect immunofluorescent test in the circulation of 100% of the 62 patients with clinical trichinellosis and 46% of the 39 patients with suspected exposure. The presence of antibodies specific to excretory-secretory products of T. spiralis muscle larvae was confirmed in the majority of the samples tested by a monoclonal antibody-based competitive inhibition assay. These results indicate that antibody detection is a more sensitive diagnostic method for human trichinellosis, but that antigen detection might be a useful confirmatory test because it is a direct demonstration of parasite products in the circulation

  15. Journalism as Cultures of Circulation

    Bødker, Henrik


    The universe of journalism has always consisted of interspersed texts, meanings and practices. Yet, much journalism research has often isolated either texts and/or contexts and as such assumed relations between professional practices, informed (rational) readers and (conceived) core texts...... of journalism. It is, however, more important than ever to shift attention away from texts to the processes through which they are circulated. This is partly because the many cultural forms of journalism (textual, institutional, technological, material, behavioural and imagined) are undergoing significant......, likes, comments, searches, journalist roles, writing and reading positions and identities etc. Such forms will be traced within the mediation of a specific event with the overall aim of beginning a theorization of the landscape of journalism as highly interrelated cultures of circulation....

  16. Proper Sizing of Circulation Pumps

    Tommerup, Henrik M.; Nørgaard, Jørgen


    The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust, but the...... results can be applied to Europe in general. Despite the small sample of houses involved in the test, 15 houses, some rather safe conclusions can be drawn from the results, which showed that newly developed pumps with power consumption around 5-8 W, can perform the task of circulating the water...... sufficiently to keep the houses satisfactorily warm during the heating season of the test. The old replaced pumps used 5-10 times more power. In Europe alone, a gradual replacement of the present vastly oversized pumps with such small but sufficient pumps can save the construction of 17 large power plants as...

  17. Radioisotopic evaluation of portal circulation

    The use of a radio-tracer of portal circulation through the intestine, should prevent cruel punctures in the portal-vein or spleen as it is usually the case with traditional methods in the study of portal-system. The absorption of I-131 and Tc-99m, previously cheked in rabbits presented similar results in dogs. The time of circulation between terminal large-intestine and the liver (t-RF) was determined by external counting at hepatic level by recording radioactivity variation-time. In healthy animals the t-RF was from 20to 60 seconds, with average time of 42 seconds. In 2 animals with partial binding of portal-vein the t-RF went up to 110 and 120 seconds. (Author)

  18. Ocean circulation generated magnetic signals

    Manoj, C.; Kuvshinov, A.; Maus, S.;


    Conducting ocean water, as it flows through the Earth's magnetic field, generates secondary electric and magnetic fields. An assessment of the ocean-generated magnetic fields and their detectability may be of importance for geomagnetism and oceanography. Motivated by the clear identification of...... ocean tidal signatures in the CHAMP magnetic field data we estimate the ocean magnetic signals of steady flow using a global 3-D EM numerical solution. The required velocity data are from the ECCO ocean circulation experiment and alternatively from the OCCAM model for higher resolution. We assume an...... magnetic field, as compared to the ECCO simulation. Besides the expected signatures of the global circulation patterns, we find significant seasonal variability of ocean magnetic signals in the Indian and Western Pacific Oceans. Compared to seasonal variation, interannual variations produce weaker signals....

  19. The Sun's Shallow Meridional Circulation

    Hathaway, David H


    The Sun's global meridional circulation is evident as a slow poleward flow at its surface. This flow is observed to carry magnetic elements poleward - producing the Sun's polar magnetic fields as a key part of the 11-year sunspot cycle. Current theories for the sunspot cycle assume that this surface flow is part of a circulation which sinks inward at the poles and turns equatorward at depths below 100 Mm. Here we use the advection of the Sun's convection cells by the meridional flow to map the flow velocity in latitude and depth. Our measurements show the largest cells clearly moving equatorward at depths below 35 Mm - the base of the Sun's surface shear layer. This surprisingly shallow return flow indicates the need for substantial revisions to solar/stellar dynamo theory.

  20. Natural circulation systems: advantages and challenges

    This lecture briefly explains the principle of working of a natural circulation system, its various advantages and applications in nuclear and other industries. The major challenges to be overcome before the wide acceptance of natural circulation as the normal mode of coolant circulation in nuclear power reactors are briefly described. Classification of NCSs and the terminologies commonly encountered in natural circulation literature are also briefly explained. (author)

  1. The general circulation of the atmosphere

    Schneider, Tapio


    Theories of how Earth's surface climate may change in the future, of how it may have been in the past, and of how it is related to climates of other planets must build upon a theory of the general circulation of the atmosphere. The view of the atmospheric general circulation presented here focuses not on Earth's general circulation as such but on a continuum of idealized circulations with axisymmetric flow statistics. Analyses of observational data for Earth's atmosphere, simulations with ide...

  2. Conservation of circulation in magnetohydrodynamics

    Bekenstein; Oron


    We demonstrate at both the Newtonian and (general) relativistic levels the existence of a generalization of Kelvin's circulation theorem (for pure fluids) that is applicable to perfect magnetohydrodynamics. The argument is based on the least action principle for magnetohydrodynamic flow. Examples of the new conservation law are furnished. The new theorem should be helpful in identifying new kinds of vortex phenomena distinct from magnetic ropes or fluid vortices. PMID:11089118

  3. Electronic circulation of accounting documents

    Kremláčková, Kateřina


    This thesis describes a circulation of accounting documents in an accounting entity, deals with legal requirements of the entire process and discusses it as a part of an internal control system of the entity. In connection with the theme of the work there are also defined legislative conditions for using information and communication technologies and introduced possibilities of involving these technologies in the process of processing of the accounting documents. Above all the electronic data...

  4. Purchase, circulation and fuel taxation

    Potter, Stephen


    During the last decade, the UK and many other developed nations have reformed existing forms of road transport taxation to address a number of transport policy goals. This has involved modifying the design of purchase, circulation and fuel taxation to promote: • More fuel efficient vehicles • Alternative fuel vehicles • Cleaner fuels (lower emissions and/or low carbon) • Modal shift and traffic volume • Congestion reduction This chapter particularly explores the use of...

  5. Identifying cancer origin using circulating tumor cells.

    Lu, Si-Hong; Tsai, Wen-Sy; Chang, Ying-Hsu; Chou, Teh-Ying; Pang, See-Tong; Lin, Po-Hung; Tsai, Chun-Ming; Chang, Ying-Chih


    Circulating tumor cells (CTCs) have become an established clinical evaluation biomarker. CTC count provides a good correlation with the prognosis of cancer patients, but has only been used with known cancer patients, and has been unable to predict the origin of the CTCs. This study demonstrates the analysis of CTCs for the identification of their primary cancer source. Twelve mL blood samples were equally dispensed on 6 CMx chips, microfluidic chips coated with an anti-EpCAM-conjugated supported lipid bilayer, for CTC capture and isolation. Captured CTCs were eluted to an immunofluorescence (IF) staining panel consisting of 6 groups of antibodies: anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20/anti-CDX2, and anti-PSA/anti-PSMA. Cancer cell lines of lung (H1975), colorectal (DLD-1, HCT-116), and prostate (PC3, DU145, LNCaP) were selected to establish the sensitivity and specificity for distinguishing CTCs from lung, colorectal, and prostate cancer. Spiking experiments performed in 2mL of culture medium or whole blood proved the CMx platform can enumerate cancer cells of lung, colorectal, and prostate. The IF panel was tested on blood samples from lung cancer patients (n = 3), colorectal cancer patients (n = 5), prostate cancer patients (n = 5), and healthy individuals (n = 12). Peripheral blood samples found panCK(+) and CK18(+) CTCs in lung, colorectal, and prostate cancers. CTCs expressing CK7(+) or TTF-1(+), (CK20/ CDX2)(+), or (PSA/ PSMA)(+) corresponded to lung, colorectal, or prostate cancer, respectively. In conclusion, we have designed an immunofluorescence staining panel to identify CTCs in peripheral blood to correctly identify cancer cell origin. PMID:26828696

  6. Examples of natural circulation in PHWR

    The main objective of this lecture is to provide deep insight into the complex natural circulation phenomena in the core of a Pressurised Heavy Water Reactor. A detailed account of natural circulation tests conducted in an Indian PHWR is given in this lecture. This will enable the participants to appreciate the importance of natural circulation in a nuclear reactor to a greater extent. (author)

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

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


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

  8. Antibody Glossary —

    The components of the immune system have diverse roles in the initial development of cancers, progression of early-stage malignancies to invasive tumors, establishment of metastatic lesions, tumor dormancy, and response or resistance to therapy. Characterizing the components of the immune system and their functional status in tissues and in tumors requires the use of highly specific reagents. Researchers employ antibodies in a variety of in vitro and in vivo applications to delineate, enrich, or deplete specific immune subsets in order to understand their role(s) in tumorigenesis. This is a glossary of validated reagents and protocols that are useful for functional phenotyping of the immune system in murine cancer models.

  9. The antibody Hijikata Tatsumi

    Éden Peretta


    Full Text Available Considered one of the most influential modern dance representatives in Japan, Tatsumi Hijikata’s work was a milestone in the Japanese post-war experimental artistic scene. Heretic son of his time, he staged a fertile mix of artistic and cultural influences, overlapping subversive elements of European arts and philosophy with radical references from pre-modern Japanese culture. In this way he built the foundations of its unstable antibody, its political-artistic project of dissolution of a organism, both physical and social.


    S. Saidi


    Full Text Available One hundred sera from children 1 - 6 years of age, representative of a large serum collection, were tested for the prevalence of antibodies against different viruses. Hemagglutination-inhibition (HI antibodies were found in 68% for measles; 61 % for rubella; 75'% for influenza A2/Hong Kong/68, 16% for influenza B/Md./59, 0% for group A arboviruses, 10% for group B arboviruses, 3% for phlebotomus fever group and 4% for Congo-Crimean hemorrhagic fever (C-CHF group of arboviruses Poliomyelitis-neutralizing antibodies for type 1, 2 and 3 were 90%; 85% and 84%~ respectively. Antibody to EH virus was detected in 84% of the sera by immuno-fluorescence. None of the sera were positive for hepatitis-B antigen or antibody by immuno-precipitation test. The prevalence of some viral antibodies found in this survey are compared with results obtained from surveys in other parts of the country.

  11. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors.

    Yu, Xiaocong; Tsibane, Tshidi; McGraw, Patricia A; House, Frances S; Keefer, Christopher J; Hicar, Mark D; Tumpey, Terrence M; Pappas, Claudia; Perrone, Lucy A; Martinez, Osvaldo; Stevens, James; Wilson, Ian A; Aguilar, Patricia V; Altschuler, Eric L; Basler, Christopher F; Crowe, James E


    Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era. Recent work has recovered the gene sequences of this unusual strain, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes. However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure-well into the tenth

  12. Serotype Specificity of Antibodies against Foot-and-Mouth Disease Virus in Cattle in Selected Districts in Uganda

    Mwiine, F.N.; Ayebazibwe, C.; Olaho-Mukani, W.;


    Uganda had an unusually large number of foot-and-mouth disease (FMD) outbreaks in 2006, and all clinical reports were in cattle. A serological investigation was carried out to confirm circulating antibodies against foot-and-mouth disease virus (FMDV) by ELISA for antibodies against non-structural......Uganda had an unusually large number of foot-and-mouth disease (FMD) outbreaks in 2006, and all clinical reports were in cattle. A serological investigation was carried out to confirm circulating antibodies against foot-and-mouth disease virus (FMDV) by ELISA for antibodies against non......-structural proteins and structural proteins. Three hundred and forty-nine cattle sera were collected from seven districts in Uganda, and 65% of these were found positive for antibodies against the non-structural proteins of FMDV. A subset of these samples were analysed for serotype specificity of the identified...... antibodies. High prevalences of antibodies against non-structural proteins and structural proteins of FMDV serotype O were demonstrated in herds with typical visible clinical signs of FMD, while prevalences were low in herds without clinical signs of FMD. Antibody titres were higher against serotype O than...

  13. The kinetics of donor HLA class I-specific antibody absorption following a combined split liver and kidney transplant

    Key, Tim; Watson, Christopher J.; Menna R. Clatworthy; O'Rourke, Cheryl M.; Goodman, Reyna S; Taylor, Craig J.; Butler, Andrew J.


    Hyperacute rejection of a transplanted liver is rare even when the recipient has circulating donor-specific alloantibodies (DSA). There is also evidence that a transplanted liver may provide immunological protection for other organs transplanted from the same donor. We monitored the kinetics of circulating DSA in a highly sensitized recipient of a combined split liver and kidney transplant and demonstrated a reduction in antibody titres immediately after liver perfusion. The absorption of DSA...

  14. Antibodies to watch in 2015

    Reichert, Janice M


    The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. As discussed in this perspective on antibodies in late-stage development, the outlook for additional approvals, potentially still in 2014 and certainly in 2015, is excellent as marketing applications for 6 antibody therapeutics (sec...

  15. Monoclonal antibodies for treating cancer

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

  16. Metrics for antibody therapeutics development

    Reichert, Janice M


    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approv...

  17. Empowered Antibody Therapies - IBC conference.

    Herold, Jens


    The Empowered Antibody Therapies conference, held in Burlingame, CA, USA, included topics covering new therapeutic developments in the field of multispecific antibodies. This conference report highlights selected presentations on DVD-Igs from Abbott Laboratories, ImmTACs from Immunocore, 'Dock-and-Lock' technology from Immunomedics, the bispecific BiTE antibody blinatumomab from Micromet, and Triomabs from TRION Pharma and Fresenius Biotech. PMID:20878591

  18. Antibody informatics for drug discovery

    Shirai, Hiroki; Prades, Catherine; Vita, Randi;


    infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... (iii) antibody numbering and IMGT. Here, we review “antibody informatics,” which may integrate the above three fields so that bridging the gaps between industrial needs and academic solutions can be accelerated. This article is part of a Special Issue entitled: Recent advances in molecular engineering...

  19. Tumor imaging with monoclonal antibodies

    Many monoclonal antibodies directed against tumor-associated antigens have been identified, but so far none of these are tumor specific. Polyclonal and monoclonal antibodies have been used for imaging of a wide variety of tumors with success. Radiolabeling of antibody is usually done with iodine isotopes of which 123I is the best candidate for radioimmunodetection purposes. The labeling of antibodies through chelates makes it possible to use metal radioisotopes like 111In, which is the best radioisotope for imaging with monoclonal antibodies due to its favorable half-life of 2.5 days. Usually imaging cannot be performed within 24 h after injection, but clearance of antibody can be increased by using F(ab)2 of Fab. Another approach is to clear non-bound antibody by a second antibody, directed against the first. The detection limit of immunoimaging is about 2 cm, but will be improved by tomography or SPECT. There is still a high false positive and false negative rate, which makes it impossible to use radioimmunodetection as the only technique for diagnosis of tumors. In combination with other detection techniques, tumor imaging with monoclonal antibodies can improve diagnosis. 44 refs.; 3 tabs

  20. Circulating follistatin in relation to energy metabolism.

    Hansen, Jakob Schiøler; Plomgaard, Peter


    Recently, substantial evidence has emerged that the liver contributes significantly to the circulating levels of follistatin and that circulating follistatin is tightly regulated by the glucagon-to-insulin ratio. Both observations are based on investigations of healthy subjects. These novel findings challenge the present view of circulating follistatin in human physiology, being that circulating follistatin is a result of spill-over from para/autocrine actions in various tissues and cells. Follistatin as a liver-derived protein under the regulation of glucagon-to-insulin ratio suggests a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated with elevated levels of circulating follistatin have a metabolic denominator with decreased insulin sensitivity and/or hyperglucagoneimia. PMID:27264073

  1. Creating Ordered Antibody Arrays with Antibody-Polymer Conjugates

    Dong, Xuehui; Obermeyer, Allie; Olsen, Bradley

    Antibodies are a category of functional proteins that play crucial roles in the immune system and have been widely applied in the area of cancer therapeutics, targeting delivery, signal detection, and sensors. Due to the extremely large size and lack of specific functional groups on the surface, it is challenging to functionalize antibodies and manipulate the ordered packing of antibodies in an array with high density and proper orientation, which is critical to achieve outstanding performance in materials. In this work, we demonstrate an efficient and facile approach for preparing antibody-polymer conjugates with two-step sequential ``click'' reaction to form antibody-polymer block copolymers. Highly ordered nanostructures are fabricated based on the principles of block copolymer self-assembly. The nanostructures are studied with both small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). Lamellae with alternating antibody domain and polymer domain are observed with an overall domain size of ~50 nm. The nanostructure not only increases the packing density and promotes proper orientation of the antibody, but also provides possible channel to facilitate substrate transportation and improves the stability of the antibody.

  2. [Circulating immune complexes in the pathogenesis of recurrent erysipelas].

    Frolov, A F; Rychnev, V E; Frolov, V M; Bala, M A


    The dynamics of circulating immune complexes (CIC) in comparison with the level of SH-groups of serum deproteinate and other characteristics of cell-mediated and humoral immunity (the reaction of the inhibition of antibodies, the levels of T-cells and their main subpopulations) was studied in 103 erysipelas patients and in 46 persons having had the disease at the acute period of this infection and at the periods between relapses. The elevated levels of CIC and SH-groups of serum deproteinate were found to be directly correlated with the inhibition index. The study showed that, as a rule, in patients with the elevated level of CIC the frequently relapsing form of erysipelas, accompanied by the formation of relative hypersuppressor-type secondary immunodeficiency and by a decrease in the functional activity of dermal macrophages, was observed. PMID:2936048

  3. Linkers Having a Crucial Role in Antibody-Drug Conjugates.

    Lu, Jun; Jiang, Feng; Lu, Aiping; Zhang, Ge


    Antibody-drug conjugates (ADCs) comprised of a desirable monoclonal antibody, an active cytotoxic drug and an appropriate linker are considered to be an innovative therapeutic approach for targeted treatment of various types of tumors and cancers, enhancing the therapeutic parameter of the cytotoxic drug and reducing the possibility of systemic cytotoxicity. An appropriate linker between the antibody and the cytotoxic drug provides a specific bridge, and thus helps the antibody to selectively deliver the cytotoxic drug to tumor cells and accurately releases the cytotoxic drug at tumor sites. In addition to conjugation, the linkers maintain ADCs' stability during the preparation and storage stages of the ADCs and during the systemic circulation period. The design of linkers for ADCs is a challenge in terms of extracellular stability and intracellular release, and intracellular circumstances, such as the acid environment, the reducing environment and cathepsin, are considered as the catalysts to activate the triggers for initiating the cleavage of ADCs. This review discusses the linkers used in the clinical and marketing stages for ADCs and details the fracture modes of the linkers for the further development of ADCs. PMID:27089329

  4. Antiphospholipid antibodies and infertility.

    Chighizola, C B; de Jesus, G R


    Since the late 1980s some publications have proposed that antiphospholipid antibodies (aPL) may have some relationship with infertility, considering reported deleterious effects that aPL exert on trophoblast proliferation and growth. Although not included in current classification criteria for antiphospholipid syndrome, many physicians investigate for aPL in patients with a history of infertility, including antibodies not listed in classification criteria, and most of those patients will receive anticoagulant therapy if any of those antibodies have a result considered positive. A review of literature was conducted searching for studies that investigated the association of aPL and infertility and if aPL positivity alters in vitro fertilization (IVF) outcome. The definition of infertility, routine work-up to exclude other causes of infertility, definition of IVF failure as inclusion criteria and control populations were heterogeneous among studies. Most of them enrolled women over 40 years of age, and exclusion of other confounding factors was also inconsistent. Of 29 studies that assessed aPL positivity rates in infertile women, the majority had small sample sizes, implying a lack of power, and 13 (44.8%) reported higher frequency of aPL in infertile patients compared to controls, but most of them investigated a panel of non-criteria aPL tests, whose clinical significance is highly controversial. Only two studies investigated all three criteria tests, and medium-high titer of anticardiolipin cut-off conforming to international guidelines was used in one study. Considering IVF outcome, there was also disparity in this definition: few studies assessed the live birth rate, others the implantation rate. Of 14 publications that addressed the relationship between aPL and IVF outcome, only two described a detrimental effect of these autoantibodies. In conclusion, available data do not support an association between aPL and infertility, and aPL positivity does not seem to

  5. Intestinal circulation during inhalation anesthesia

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86Rb and 9-microns spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO2) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  6. Targeting of Antibodies using Aptamers

    Missailidis, Sotiris


    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  7. Refolding Technologies for Antibody Fragments

    Tsutomu Arakawa; Daisuke Ejima


    Refolding is one of the production technologies for pharmaceutical grade antibody fragments. Detergents and denaturants are primarily used to solubilize the insoluble proteins. The solubilized and denatured proteins are refolded by reducing the concentration of the denaturants or detergents. Several refolding technologies have been used for antibody fragments, comprising dilution, dialysis, solid phase solvent exchange and size exclusion chromatography, as reviewed here. Aggregation suppresso...


    Gholamreza Pourmand


    Full Text Available Two hundred and forty patients, who had undergone vasectomy from 1977 to 1985 and subsequent vasovasostomy ,were studied for the presence of sperm-specific antibodies by using the Kibrick's gelatin agglutination test. The number of successful pregnancies and the presence of agglutination were also considered in this survey. Sixty-nine pregnancies occurred in total and agglutination was present in 49% out of 51% positive specimens by the Kibrick Test."nThe average sperm motility was slightly higher in the negative Kibrick group than in the positive Kibrick group. The obtained data indicated that there seems to be a relationship between the increased titers and percentage of agglutination in semen samples.

  9. Metrics for antibody therapeutics development.

    Reichert, Janice M


    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed. PMID:20930555

  10. Epstein-Barr virus antibody test

    EBV antibody test; EBV serology ... a lab, where a lab specialist looks for antibodies to the Epstein-Barr virus. In the first stages of an illness, little antibody may be detected. For this reason, the test ...

  11. Measurement of antibodies to tubulin by radioimmunoassay

    A solid-phase double antibody radioimmunoassay capable of measuring antibody to tubulin, the principal component of microtubules, is described. This assay is simple, combining sensitivity with specificity and also allowing determination of antibody subclasses. (Auth.)

  12. Antibodies - Office of Cancer Clinical Proteomics Research

    NCI announces the release of monoclonal antipeptide antibodies from rabbit for distribution on the antibody portal. There are 60 recently added monoclonal antibodies, with 56 generated from mouse and 4 generated from rabbit.

  13. Improved radioimmunoscintigraphy of human mammary carcinoma xenografts after injection of an anti-antibody

    The low tumor-to-background ratio obtained after administration of radiolabeled whole monoclonal antibodies (MAbs) is one of the major problems in immunoscintigraphy and -therapy. To reduce the blood pool label caused by the circulation of radiolabeled MAb we have investigated the advantage of injecting an anti-antibody after administration of tumor-specific MAb in nude mice bearing human mammary carcinoma xenografts. The MAb MA 10-11 of rat origin, used in these studies, had shown a high affinity to human mammary carcinoma tissue on frozen sections and low cross-reactivity with various normal human tissues. 24 h after injection of 1.5 MBq 131I-labeled MAb containing 10 μg IgG2a one group of mice received an additional injection of 100 μg anti-rat antibody. Blood taken 2 min after the second antibody injection showed nearly the whole activity bound to antibody aggregates, that cleared very rapidly from the circulation and accumulated in liver and spleen. The transitory high liver activity decreased within several hours because of rapid deiodination of the antibody-complex in this organ. The release of radioactivity from the spleen, however, was found to be much slower. The rapid excretion of the radioactivity from the blood pool combined with a nearly constant tumor activity allowed early tumor detection with tumor-to-blood ratios of 250:1 at 48 h after anti-antibody injection compared to 1.1:1 obtained for the control animals. In addition the results may explain the reported reduction of imaging quality and high uptake of radioactivity in the spleen of patients having repeated injections of mouse MAbs due to complex formation after development of human anti-mouse antibodies. (orig.)

  14. A two-site immunoradiometric assay for human pregnancy-associated plasma protein A (PAPP-A) using monoclonal antibodies

    A rapid, sensitive immunoradiometric assay has been developed for human pregnancy-associated plasma protein A (PAPP-A) using a purified mouse monoclonal antibody as the tracer and a rabbit polyclonal antibody to this protein in the solid-phase antibody preparation. The assay showed no measurable cross-reaction (< 0.1%) against a range of purified human placental proteins, and a good correlation with a previously described radioimmunoassay procedure when tested on samples taken throughout normal human pregnancies. No PAPP-A-like immunological activity could be detected in sera from non-pregnant women, confirming the absence of this protein from the circulation outside pregnancy. (Auth.)

  15. A blood circulation model for reference man

    Leggett, R.W.; Eckerman, K.F. [Oak Ridge National Lab., TN (United States). Health Sciences Research Div.; Williams, L.R. [Indiana Univ., South Bend, IN (United States). Div. of Liberal Arts and Sciences


    This paper describes a dynamic blood circulation model that predicts the movement and gradual dispersal of a bolus of material in the circulation after its intravascular injection into an adult human. The main purpose of the model is to improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The total blood volume is partitioned into the blood contents of 24 separate organs or tissues, right heart chambers, left heart chambers, pulmonary circulation, arterial outflow to the systemic tissues (aorta and large arteries), and venous return from the systemic tissues (large veins). As a compromise between physical reality and computational simplicity, the circulation of blood is viewed as a system of first-order transfers between blood pools, with the delay time depending on the mean transit time across the pool. The model allows consideration of incomplete, tissue-dependent extraction of material during passage through the circulation and return of material from tissues to plasma.

  16. Isolation and characterization of circulating tumor cells in prostate cancer

    Elan Shlomo Diamond


    Full Text Available Circulating tumor cells (CTCs are tumor cells found in the peripheral blood that originate from established sites of malignancy and likely have metastatic potential. Analysis of circulating tumor cells CTCs has shown great promise as a prognostic marker as well as a potential source of novel therapeutics. Isolation and characterization these cells for study, however, remain challenging due to their rarity in comparison with other cellular components of peripheral blood. Several techniques that exploit the unique biochemical properties of CTCs have been developed to facilitate isolation of these cells. Positive selection of CTCs is achieved using microfluidic surfaces coated with antibodies against epithelial cell markers or tumor specific antigens such as EpCAM or prostate specific membrane antigen (PSMA. Following isolation, characterization of CTCs may help guide clinical decision-making. For instance, molecular and genetic characterization may shed light on the development of chemotherapy resistance and mechanisms of metastasis without the need for tissue biopsy. This paper will review novel isolation techniques to capture CTCs from patients with advanced cancers, as well as efforts to characterize the CTCs. We will also review ways in which these analyses can assist in clinical decision-making,Conclusion: The study of CTCs provides insight into the molecular biology of their tumors of origin that will eventually guide the development tailored therapeutics. These advances are predicated on high yield and accurate isolation techniques that exploit the unique biochemical features of these cells.

  17. Cardiovascular complications and increased levels of circulating modified low density lipoprotein in HIV patients and patients with lipodystrophy

    K.R.O.M. Ronchini


    Full Text Available The introduction of highly active antiretroviral therapy (HAART for patients infected with HIV has significantly prolonged the life expectancy and to some extent has restored a functional immune response. However, the premature introduction of HAART has led to a significant and alarming increase in cardiovascular complications, including myocardial infarction and the appearance of abnormal distribution of body fat seen as lipodystrophy. One key element in the development of ischemic coronary artery disease is the presence of circulating and tissue-fixed modified low density lipoprotein (mLDL that contributes to the initiation and progression of arterial lesions and to the formation of foam cells. Even though not completely elucidated, the most likely mechanism involves mLDL in the inflammatory response and the induction of a specific immune response against mLDL. Circulating antibodies against mLDL can serve as an indirect marker of the presence of circulating and vessel-fixed mLDL. In the present study, we measured antibodies to mLDL and correlated them with immune status (i.e., number of CD4+ T cells in 59 HIV patients and with the clinical manifestation of lipodystrophy in 10 patients. We observed a significant reduction in anti-mLDL antibody levels related both to lipodystrophy and to an immunocompromised state in HIV patients. We speculate that these antibodies may explain in part the rapid development of ischemic coronary artery disease in some patients.

  18. Circulation of Venus upper mesosphere.

    Zasova, Ludmila; Gorinov, Dmitry; Shakun, Alexey; Altieri, Francesca; Migliorini, Alessandra; Piccioni, Giuseppe; Drossart, Pierre


    Observation of the O2 1.27 μm airglow intensity distribution on the night side of Venus is one of the methods of study of the circulation in upper mesosphere 90-100 km. VIRTIS-M on board Venus Express made these observations in nadir and limb modes in Southern and Northern hemispheres respectively. Global map of the O2 night glow is published (Piccioni et al. 2009). In this work we use for analysis only data, obtained with exposure > 3 s to avoid high noisy data. It was found that intensity of emission decreases to poles and to terminators (similar to Piccioni et al.2009) in both hemispheres, which gives evidence for existence of SS-AS circulation with transport of the air masses through poles and terminators with ascending/descending flows at SS/AS areas. However, asymmetry of distribution of intensity of airglow is observed in both hemispheres. Global map for southern hemisphere (from nadir data) has good statistics at φ > 10-20° S and pretty poor at low latitude. Maximum emission is shifted from midnight by 1 - 2 hours to the evening (22-23h) and deep minimum of emission is found at LT=2-4 h at φ > 20° S. This asymmetry is extended up to equatorial region, however statistic is poor there. No evident indication for existence of the Retrograde Zonal Superrotation (RZS) is found: maximum emission in this case, which is resulting from downwards flow, should be shifted to the morning. The thermal tides, gravity waves are evidently influence on the night airglow distribution. VIRTIS limb observations cover the low northern latitudes and they are more sparse at higher latitudes. Intensity of airglow at φ = 0 - 20° N shows wide maximum, which is shifted by 1- 2 h from midnight to morning terminator. This obviously indicates that observed O2 night glow distribution in low North latitudes is explained by a superposition of SS-AS flow and RZS circulation at 95-100 km. This behavior is similar to the NO intensity distribution, obtained by SPICAV.

  19. Nanotechnology for the detection and kill of circulating tumor cells

    Gao, Yang; Yuan, Zhou


    Circulating tumor cells (CTCs) represent a surrogate biomarker of hematogenous metastases and thus could be considered as a `liquid biopsy' which reveals metastasis in action. But it is absolutely a challenge to detect CTCs due to their extreme rarity. At present, the most common principle is to take advantage of the epithelial surface markers of CTCs which attach to a specific antibody. Antibody-magnetic nanobeads combine with the epithelial surface markers, and then the compound is processed by washing, separation, and detection. However, a proportion of CTC antigen expressions are down-regulated or lost in the process of epithelial-mesenchymal transition (EMT), and thus, this part of CTCs cannot be detected by classical detection methods such as CellSearch. To resolve this problem, some multiple-marker CTC detections have been developed rapidly. Additionally, nanotechnology is a promising approach to kill CTCs with high efficiency. Implantable nanotubes coated with apoptosis-promoting molecules improve the disease-free survival and overall survival. The review introduces some novel CTC detection techniques and therapeutic methods by virtue of nanotechnology to provide a better knowledge of the progress about CTC study.

  20. A reliable method to concentrate circulating DNA.

    Bryzgunova, Olga; Bondar, Anna; Morozkin, Evgeniy; Mileyko, Vladislav; Vlassov, Valentin; Laktionov, Pavel


    Concentration of circulating DNA probes is required to increase the amount of DNA involved in subsequent study (by polymerase chain reaction, sequencing, and microarray). This work was dedicated to the comparison of five different methods used for concentration of DNA circulating in blood. Precipitation of circulating DNA with acetone in the presence of triethylamine provides minimal DNA loss, high reproducibility, and at least three times higher DNA yield in comparison with the standard ethanol protocol. PMID:20828533

  1. Space-Time Radar Waveforms: Circulating Codes

    Babur, G.; Aubry, P.; Le Chevalier, F.


    This paper describes a concept of the circulating codes covering the whole class of the space-time codes. The circulating codes do not narrow the radiated pattern of the antenna array, thus providing a wide angular coverage, possibly tunable. In turn, the beam-forming on transmit is achievable by means of the signal processing in one (or each) receiver channel. The modelling results demonstrate the efficiency of the circulating codes based on their multidimensional ambiguity functions.

  2. Linear thermal circulator based on Coriolis forces.

    Li, Huanan; Kottos, Tsampikos


    We show that the presence of a Coriolis force in a rotating linear lattice imposes a nonreciprocal propagation of the phononic heat carriers. Using this effect we propose the concept of Coriolis linear thermal circulator which can control the circulation of a heat current. A simple model of three coupled harmonic masses on a rotating platform permits us to demonstrate giant circulating rectification effects for moderate values of the angular velocities of the platform. PMID:25768443

  3. The Ten Relationships in Rural Land Circulation

    Cai, Zhirong; Ren, Shuo; Zhang, Zhigang


    The ten relationships during land circulation are discussed. Among them, the relationship between peasant household and government indicates that government should only carry out its service and regulatory functions and farmers should be the main body of land circulation, because peasants usually have no discourse power during land circulation. In the relationship between land ownership and contracting management right, we mainly discuss the transfer of land contracting management right and p...

  4. Role of Circulating Fibrocytes in Cardiac Fibrosis

    Lin, Rong-Jie; Su, Zi-Zhuo; Liang, Shu-Min; Chen, Yu-Yang; Shu, Xiao-Rong; Nie, Ru-Qiong; Wang, Jing-Feng; Xie, Shuang-Lun


    Objective: It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis. Data Sources: This review is based on the data from 1994 to present obtained from PubMed. The search terms were “circulating fibrocytes” and “cardiac fibrosis”. Study Selection: Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected. Results: Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts. Conclusions: Circulating fibrocytes are effector cells in cardiac fibrosis. PMID:26831236

  5. Improvement of Classification of Enterprise Circulating Funds

    Rohanova Hanna O.


    Full Text Available The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, which clearly shows the role of circulating funds in managing enterprise finance and economy in general. The article supplements and groups classification features of enterprise circulating funds by: the organisation level, functioning character, sources of formation and their cost, and level of management efficiency. The article shows that the provided grouping of classification features of circulating funds allows exerting all-sided and purposeful influence upon indicators of efficiency of circulating funds functioning and facilitates their rational management in general. The prospect of further studies in this direction is identification of the level of attraction of loan resources by production enterprises for financing circulating funds.

  6. A blood circulation model for reference man

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86

  7. Generation of anti-idiotype scFv for pharmacokinetic measurement in lymphoma patients treated with chimera anti-CD22 antibody SM03.

    Qi Zhao

    Full Text Available Pre-clinical and clinical studies of therapeutic antibodies require highly specific reagents to examine their immune responses, bio-distributions, immunogenicity, and pharmacodynamics in patients. Selective antigen-mimicking anti-idiotype antibody facilitates the assessment of therapeutic antibody in the detection, quantitation and characterization of antibody immune responses. Using mouse specific degenerate primer pairs and splenocytic RNA, we generated an idiotype antibody-immunized phage-displayed scFv library in which an anti-idiotype antibody against the therapeutic chimera anti-CD22 antibody SM03 was isolated. The anti-idiotype scFv recognized the idiotype of anti-CD22 antibody and inhibited binding of SM03 to CD22 on Raji cell surface. The anti-idiotype scFv was subsequently classified as Ab2γ type. Moreover, our results also demonstrated firstly that the anti-idiotype scFv could be used for pharmacokinetic measurement of circulating residual antibody in lymphoma patients treated with chimera anti-CD22 monoclonal antibody SM03. Of important, the present approach could be easily adopted to generate anti-idiotype antibodies for therapeutic antibodies targeting membrane proteins, saving the cost and time for producing a soluble antigen.

  8. Irregular Labellings of Circulant Graphs

    Anholcer, Marcin


    We investigate the \\textit{irregularity strength} ($s(G)$) and \\textit{total vertex irregularity strength} ($tvs(G)$) of circulant graphs $Ci_n(1,2,...,k)$ and prove that $tvs(Ci_n(1,2,...,k))=\\lceil\\frac{n+2k}{2k+1}\\rceil$, while $s(Ci_n(1,2,...,k))=\\lceil\\frac{n+2k-1}{2k}\\rceil$ except the case when $(n \\bmod 4k = 2k+1 \\wedge k\\bmod 2=1) \\vee n=2k+1$ and $s(Ci_n(1,2,...,k))=\\lceil\\frac{n+2k-1}{2k}\\rceil+1$.

  9. Inflammatory response and extracorporeal circulation.

    Kraft, Florian; Schmidt, Christoph; Van Aken, Hugo; Zarbock, Alexander


    Patients undergoing cardiac surgery with extracorporeal circulation (EC) frequently develop a systemic inflammatory response syndrome. Surgical trauma, ischaemia-reperfusion injury, endotoxaemia and blood contact to nonendothelial circuit compounds promote the activation of coagulation pathways, complement factors and a cellular immune response. This review discusses the multiple pathways leading to endothelial cell activation, neutrophil recruitment and production of reactive oxygen species and nitric oxide. All these factors may induce cellular damage and subsequent organ injury. Multiple organ dysfunction after cardiac surgery with EC is associated with an increased morbidity and mortality. In addition to the pathogenesis of organ dysfunction after EC, this review deals with different therapeutic interventions aiming to alleviate the inflammatory response and consequently multiple organ dysfunction after cardiac surgery. PMID:26060024

  10. The aerodynamics of circulation control

    Wood, N. J.


    Two dimensional subsonic wind tunnel tests were conducted on a 20% thickness: chord ratio circulation controlled elliptic aerofoil section equipped with forward and reverse blowing slots. Overall performance measurements were made over a range of trailing edge blowing momentum coefficients from 0 to 0.04; some included the effect of leading edge blowing. A detailed investigation of the trailing edge wall jet, using split film probes, hot wire probes and total head tubes, provided measurements of mean velocity components, Reynolds normal and shear stresses, and radial static pressure. The closure of the two dimensional angular momentum and continuity equations was examined using the measured data, with and without correction, and the difficulty of obtaining a satisfactory solution illustrated. Suggestions regarding the nature of the flow field which should aid the understanding of Coanda effect and the theoretical solution of highly curved wall jet flows are presented.

  11. Observations on the use of the various ELISA kits for the detection of antibodies against non-structural proteins of foot and mouth disease in pigs in Hong Kong

    Data is reviewed from results using different ELISA kits for the determination of antibodies to FMD NSP tests on samples from pigs. Kits had similar proficiencies for detecting antibodies. The circulation of FMD virus in vaccinated pigs in the absence of clinical disease is indicated, and this could account for the repeated infections seen in various farms in Hong Kong. (author)

  12. Seroprevalence of antibodies to Venezuelan equine encephalitis complex (subtypes IAB and VI in humans from General Belgrano Island, Formosa, Argentina

    Cámara Alicia


    Full Text Available This work presents the results of the detection of antibodies (immunoglobulin G for subtypes I and VI of VEE viruses complex (Togaviridae family in people from the General Belgrano island, Formosa province (Argentina. The prevalence of neutralizing (NT antibodies for subtype VI was from 30% to 70% and the prevalence of antibodies inhibitory of hemagglutination (HI was of 0% in the first and second inquiry respectively. For the subtype IAB the prevalence of NT antibodies was from 13% to 3.6%, similar to the prevalence total for both subtypes. HI antibodies were not detected in any inquiries for any subtype. It was observed that both subtypes circulate simultaneously, while subtype VI remains constant with some peaks, subtype I was found in low level.

  13. The presence of HLA-antibodies in recurrent miscarriage patients is associated with a reduced chance of a live birth

    Nielsen, Henriette Svarre; Witvliet, Marian D; Steffensen, Rudi;


    increases the chance that allogeneic fetal cells appear in the maternal circulation. This study investigates the frequency of HLA-antibodies in secondary RM, primary RM patients and parous controls and analyzes whether the presence of HLA-antibodies in early pregnancy is associated with pregnancy outcome......Anti-paternal HLA-antibodies are considered a harmless phenomenon during most pregnancies, whereas their role in recurrent miscarriage (RM) patients is disputed. In contrast to primary RM, patients with secondary RM have carried a fetus to term pregnancy prior to a series of miscarriages, which....... Sera from women with secondary RM (n=56), primary RM (n=13) and parous controls (n=24) were tested for HLA-antibodies using an ELISA assay and complement dependent cytotoxicity. Samples were taken at gestational week 4-5 in 62 (90%) of the patients. HLA-antibodies were significantly more frequent in...

  14. Problems in the application of labelled antibody techniques to communicable and parasitic diseases

    Two-site immunoradiometric and universal reagent techniques, using radiolabelled antibody, may be applied to communicable diseases. Labelled antibody techniques avoid the problems of purifying and then atraumatically radioiodinating the microorganismal antigens for radioimmunoassay. The application of solid-phase radiolabelled techniques to detect antigenaemia and circulating antibodies in mycobacterial diseases and amoebiasis caused by Mycobacterium tuberculosis and Entamoeba histolytica is described. Methods of antibody radioiodination (Chloramine-T, lactoperoxidase and iodogen) are compared, as well as the relative efficacy of labelling immunoglobulin sodium sulphate precipitate fractions vis-a-vis antibodies purified by affinity chromatography on antigen linked to immunoadsorbents (CNBr Sepharose 4B, diazocellulose). The problems of non-specific reactions because of interglobulin reactions or sticky IgM antibodies adhering to plastic solid phases are emphasized. Serious problems may arise if the antisera employed for labelling have themselves been raised against immunogens with complete Freund' s adjuvant because of anti-mycobacterial antibodies. A non-specific reaction in a communicable disease/infestation may represent a low level of exposure and a low level specific reaction, and the problem of obtaining non-infected non-exposed controls arises. Even neonatal blood may contain material IgG antibodies. Various methods of minimizing non-specific interglobulin reactions are stressed to obtain optimal sensitivity, as well as the need for 'matching' the specific antiserum and the universal reagent. Reference is made to the use of monoclonal antibodies derived from in vitro hybridomas in overcoming some of the problems at present limiting the labelled antibody techniques

  15. Seroprevalence of Norovirus Genogroup IV Antibodies among Humans, Italy, 2010–2011

    Di Martino, Barbara; Di Profio, Federica; Ceci, Chiara; Di Felice, Elisabetta; Kim Y Green; Bok, Karin; De Grazia, Simona; Giammanco, Giovanni M; Massirio, Ivano; Lorusso, Eleonora; Buonavoglia, Canio; Marsilio, Fulvio; Martella, Vito


    Noroviruses (NoVs) of genogroup IV (GIV) (Alphatron-like) cause infections in humans and in carnivorous animals such as dogs and cats. We screened an age-stratified collection of serum samples from 535 humans in Italy, using virus-like particles of genotypes GIV.1, circulating in humans, and GIV.2, identified in animals, in ELISA, in order to investigate the prevalence of GIV NoV-specific IgG antibodies. Antibodies specific for both genotypes were detected, ranging from a prevalence of 6.6% t...

  16. Transcriptional stalling in B-lymphocytes: a mechanism for antibody diversification and maintenance of genomic integrity.

    Sun, Jianbo; Rothschild, Gerson; Pefanis, Evangelos; Basu, Uttiya


    B cells utilize three DNA alteration strategies-V(D)J recombination, somatic hypermutation (SHM) and class switch recombination (CSR)-to somatically mutate their genome, thereby expressing a plethora of antibodies tailor-made against the innumerable antigens they encounter while in circulation. Of these three events, the single-strand DNA cytidine deaminase, Activation Induced cytidine Deaminase (AID), is responsible for SHM and CSR. Recent advances, discussed in this review article, point toward various components of RNA polymerase II "stalling" machinery as regulators of AID activity during antibody diversification and maintenance of B cell genome integrity. PMID:23584095

  17. Surveillance of antibodies to bluetongue virus in livestock in Mongolia using C-ELISA: preliminary results

    A competitive enzyme-linked immunosorbent assay (C-ELISA) was used to conduct surveillance of bluetongue virus antibodies (BTV) in sheep, goats and cattle in Mongolia. The highest prevalence was recorded in goats (86%) followed by sheep (51%) and cattle (9%). The results are the first confirmation of the presence of such antibodies in Mongolian livestock. Studies are now underway to conduct more detailed investigations concerning bluetongue, including to determine the virus serotypes that are and have been circulating in the country. (author)

  18. [Prevalence of anti-HAV antibodies (hepatitis A virus) in 18-year-old males from the Florence area].

    Calabri, G B; Santini, M G; Genovese, F; Bambi, F; Salvi, G; Calabri, G


    In 1998 sera from 430 18 year old male subjects living in "Florentina area" have been tested for anti-hepatitis A virus (HAV) antibodies. 27 out of 430, (6.2%), study samples were found to be positive. Our results confirm the low circulation rate of HAV in Florence area. PMID:10963011

  19. Heterologous challenge of weaned piglets in the presence of maternal derived antibodies results in vaccine-associated enhanced respiratory disease

    Effective vaccine immunization against influenza A viruses (IAV) in pigs in the United States is challenging because of the great antigenic diversity of co-circulating viruses. Maternally derived antibodies (MDA) interfere with vaccine efficacy and can lead to vaccine-enhanced respiratory disease (V...

  20. Maternal derived antibodies induce vaccine-associated enhanced respiratory disease in weaned pigs challenged with heterologous virus

    Introduction Effective vaccine immunization against influenza A viruses (IAV) in pigs in the United States is a challenge because of the great antigenic diversity of co-circulating viruses. Another obstacle to vaccine efficacy in pigs is the presence of maternally derived antibodies (MDA), which hav...

  1. Unit group of algebra of circulant matrices

    Rajendra Sharma


    Full Text Available Let Crn(Fp denote the algebra of nXn circulant matrices over Fp, finite field of order p of prime characteristic p. The order of the unit groups U(Cr3(Fp, U(Cr4(Fp and U(Cr5(Fp of algebras of circulant matrices over Fp are characterized.

  2. Introduction to instabilities in natural circulation systems

    This lecture reviews the various natural circulation instabilities and their classification instabilities observed during various stages of natural circulation such as single-phase, boiling inception and fully developed two-phase flow are described. The mechanisms causing the instabilities are also briefly described. (author)

  3. Kelvin's Canonical Circulation Theorem in Hall Magnetohydrodynamics

    Shivamoggi, B K


    The purpose of this paper is to show that, thanks to the restoration of the legitimate connection between the current density and the plasma flow velocity in Hall magnetohydrodynamics (MHD), Kelvin's Circulation Theorem becomes valid in Hall MHD. The ion-flow velocity in the usual circulation integral is now replaced by the canonical ion-flow velocity.

  4. Antibody fragments: Hope and hype

    Nelson, Aaron L


    The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variabl...

  5. Functional effects of anticardiolipin antibodies.

    Harris, E N; Pierangeli, S S


    The 'lupus anticoagulant' phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their 'thrombogenic effects' in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which beta 2-glycoprotein 1 (beta 2-GP1) was absent. Affinity purified aPL antibodies had 25-50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, beta 2-GPI and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important. PMID:8902763

  6. The antineutrophil antibody in uveitis.

    Young, D W


    Ninety eight patients with uveitis of various types were tested for the presence of the antineutrophil antibody or ANCA by an indirect immunofluorescence method. This antibody is found in patients with diseases associated with small vessel vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. Eleven true positive cases were found. A positive test was not associated with the anatomical site of the uveitis but was related to the time course of the disease. In particular ...

  7. Interfacial metal and antibody recognition

    Zhou, Tongqing; Hamer, Dean H.; Hendrickson, Wayne A.; Sattentau, Quentin J.; Kwong, Peter D.


    The unique ligation properties of metal ions are widely exploited by proteins, with approximately one-third of all proteins estimated to be metalloproteins. Although antibodies use various mechanisms for recognition, to our knowledge, none has ever been characterized that uses an interfacial metal. We previously described a family of CD4-reactive antibodies, the archetype being Q425. CD4:Q425 engagement does not interfere with CD4:HIV-1 gp120 envelope glycoprotein binding, but it blocks subse...

  8. Pyoderma gangrenosum and anticardiolipin antibody

    de Godoy Jose Maria


    Full Text Available Pyoderma gangrenosum (PG is a rare ulceronecrotic inflammatory cutaneous disorder and is frequently associated with systemic diseases. The authors report a 22-year-old male patient with pyoderma gangrenosum, thrombosis of both popliteal arteries, ischemic stroke and seropositivity for anticardiolipin antibody. Despite intravenous treatment with antibiotics, corticosteroid and heparin, pyoderma gangrenosum caused necrosis of his right lower limb which resulted in amputation. It was concluded that the anticardiolipin antibody may have contributed to the gravity of this case.

  9. Antibodies to watch in 2014.

    Reichert, Janice M


    Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed. PMID:24284914

  10. Tabhu: tools for antibody humanization.

    Olimpieri, Pier Paolo


    SUMMARY: Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity into a suitable human template. Unfortunately, this procedure may results in a partial or complete loss of affinity of the grafted molecule that can be restored by back-mutating some of the residues of human origin to the corresponding murine ones. This trial-and-error procedure is hard and involves expensive and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: CONTACT:, SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.