Development of a monoclonal antibody-based immunoradiometric assay for the measurement of the free alpha-subunit of human chorionic gonadotrophin.Haneef, Raazia Be. January 1990 (has links)
Almost a century has elapsed since the antigen-antibody interaction was first recognised as the basis of an immune response (Ehrlich, 1897). However, it was only in the 1930s, with the development of improved technologies that this concept was better understood, and led to the discovery of the amazing diversity and specificity of antibody molecules (Landsteiner, 1933). Theoretically, it is possible to make antibodies to a variety of biological substances and other chemicals, and therefore they are ideally suited as specific recognition elements to be used for analytical, cytological, functional, therapeutic and biochemical purposes. The development of the radioimmunoassay (RIA) thirty five years ago, revolutionised research in many areas of clinical and scientific investigation. This technique evolved rapidly from the discovery made by Berson et al. in 1956 that antibodies to insulin could be detected in patients treated with this hormone, by measuring the binding of radiolabeled insulin to these antibodies. Although in the past RIAs have been the most important assay system employing antibody and labelled tracer, the limitation was that reliance had to be placed on the chance development of a good polyclonal antibody. These shortcomings stimulated the search for monospecific antibodies of reproducible quality and sufficient quantity. The development and introduction of monoclonal antibody technology brought about a revolution in immune serology (Kohler and Milstein, 1975). Establishment of immortal cell lines which contained the genetic elements of antibody-producing cells was achieved by fusion between a myeloma cell line and spleen cells from an immunised donor. The resulting hybrids had the essential properties of both parents, namely, permanent growth and a high capacity for the synthesis and secretion of immunoglobulins, normally characteristics of plasmacytomas, together with the genetic elements defining a specific antibody. Gestational trophoblastic disease (GTD) is a neoplastic condition of the trophoblast and occurs as molar pregnancy in a benign or invasive form, or as choriocarcinoma in a malignant form. Effective therapy has been developed for the treatment of both choriocarcinoma and molar pregnancy, but the key to successful management of these patients lies in their prompt diagnosis and careful monitoring of response to treatment (Green-Thompson, 1986). Fortuitously, these tumours elaborate the human chorionic gonadotrophin hormone (hCG) and its free alpha (a) and beta (B) subunits and hence a ready marker for the tumour exists. Human chorionic gonadotrophin is one of a group of glycoprotein hormones, which includes luteinising hormone (LH), follicle stimulating hormone (FSH) and thyroid stimulating hormone (TSH). These hormones are composed of two dissimilar subunits designated a and B, which are bound non-covalently in the intact molecule. The B-subunit of each glycoprotein hormone is unique and is responsible for the respective biological and immunological properties of the glycoproteins. In contrast, all four hormones possess an identical a-subunit which is coded for by a single gene (Fiddes and Goodman, 1979). The measurement of hCG and its free B-subunit, as so-called BhCG, for the diagnosis and monitoring of therapy in patients with GTD is now routinely practised throughout the world (Vaitukaitis et al., 1972). However it has been demonstrated by Bagshawe (1975) that when serum BhCG can no longer be measured by current RIA methods, up to 10" tumour cells may remain undetected. In addition, there have been isolated reports of two patients with choriocarcinoma in whom BhCG was undetectable in the serum but who appeared to be secreting only the a-subunit (Dawood et al, 1977). Furthermore, it has been suggested that measurement of free a-subunit rather than intact hCG or the free B-subunit is a more effective means of detecting persistent trophoblastic disease as well as tumour recurrence following treatment (Quigley et al, 1980a and b). Radioimmunoassays which measure the free a-subunit of hCG have been developed, but in general lack the specificity and sensitivity required (Gaspard et al, 1980; Kohorn et al, 1981). These assays employ polyclonal antisera which also detect epitopes common to the pituitary gonadotrophins. Thus there is a need to produce monoclonal antibodies which recognise regions of the free a-subunit which are hidden in the intact gonadotrophins. Such antibodies would provide the required specificity for use in RIAs but are limited in their use by their inherent lack of high affinity for the antigen. Fortunately, this drawback may be overcome by using monoclonal antibodies as labelled reagents in an alternative assay system, the immunoradiometric assay (IRMA), described by Miles and Hales (1968). The IRMA, particularly the two-site sandwich version of the assay, has been shown to provide greater sensitivity in addition to allowing enhanced specificity. This is a consequence of the use of two antibodies in excess to detect the analyte, each directed at a different epitope on the target molecule. The first antibody, referred to as the capture antibody, is usually linked to a solid-phase to facilitate easy separation and is added in excess relative to the target hormone to enhance antibody-antigen interaction, thereby allowing increased sensitivity in the measurement of analyte. The second antibody, referred to as the detection antibody, is labelled with a radioactive isotope or an enzyme to detect antigen already bound to the capture antibody. The application of monoclonal antibodies specific for the free a-subunit to a highly sensitive IRMA format is an obvious need. Hence this study was undertaken firstly, to raise and characterise monoclonal antibodies to the free a-subunit, secondly to develop an IRMA using these antibodies and finally to establish whether measurement of free a-subunit has any clinical advantage. / Thesis (M.Med.Sc.)-University of Natal, Durban, 1990.
Evaluation of surface dose outside the treatment area for breast cancer irradiation modalities using thermoluminescence dosimeters (TLDs)Unknown Date (has links)
The purpose of this research is to compare the surface dose outside the treatment area for different breast cancer irradiation modalities using Thermoluminescence Dosimeters (TLDs). Five different modalities are included in this study: Accuboost, Photon boost, Electron boost, Strut-Adjusted Volume Implant (SAVI), and Mammosite Multi-lumen (ML).Six points of interest (POI) on the breast cancer patients had been selected for the TLDs placement. Data from 25 breast cancer patients at Lynn Cancer Institute of the Boca Raton Regional Hospital were included in the study. The measured percentage ranges of the averaged doses at the six POIs for the different modalities are: Sternum 0.26% - 3.26%, Shoulder 0.33% - 2.79%, Eye 0.26% - 1.32%, Thyroid 0.20% - 2.75%, CLB 0.2% - 5.46%, Lower Abdomen 0.16% - 2.25%. / Suraj Prasad Khanal. / Thesis (M.S.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.
Variations of Pericardial Dose at Different Respiratory Status in Accelerated Partial Breast Irradiation (APBI) Using Cyberknife M6™ Multileaf Collimators (CKMLC)Unknown Date (has links)
The purpose of this study is to investigate the changes of the pericardial dose at different respiratory phases and statuses in accelerated partial breast irradiation (APBI) using Cyberknife M6™ multileaf collimators (CK-MLC). Anonymous 6 female patient files with respiration gated four-dimensional computed tomography (4DCT) sets, and 6 left breast cancer cases with CT images in free-breathing (FB) and deep inhalation breath-hold (BH) were selected. One CT image set from each patient was planned for APBI in Accuray Multiplan™ 5.2, and respectively compared its pericardial dose with those from CT sets of other respiratory phases. All the comparable CT images were fused in the planning system according to the left chest wall, among which the lung gap anterior to the pericardium varies by the lung expansion. For the purpose of this study, the tumor volume was outlined in the media-lower quadrant of the left breast where this lung gap is relatively small. All the plans in this study met the requirements set by the National Surgical Adjuvant Breast and Bowel Project/Radiation Therapy Oncology Group (NSABP/RTOG), specifically protocol B-39/RTOG 0413. From the comparisons in this investigation, the mean relative pericardial dose of the BH CT group showed significant or 45% (p < 0.01) lower value than that of FB CT group. However, in FB 4DCT group, 3 of 6 cases indicated a meaningful reduction (p < 0.05) in 100% inhalation phase when compared with the mean dose over other phases. The inconsistent pericardial doses were displayed in FB 4DCT group due to minimal changes in the anterior lung gap of the pericardium, when the diaphragmatic breathing was dominant in those patients. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection
Njoku, Eni Gerald
Thesis. 1976. Ph.D.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. / Microfiche copy available in Archives and Engineering. / Vita. / Includes bibliographical references. / Ph.D.
Rotman, Stanley Richard
Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1979. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Includes bibliographical references. / by Stanley Richard Rotman. / B.S.
McKillop, Jordan M.
20 November 2009
The main objective of this research is: (1) to develop a model and perform numerical simulations to evaluate the radiation field and the resulting dose to personnel and activation of materials and structures throughout the IRIS nuclear power plant, and (2) to confirm that the doses are below the regulatory limit, and assess the possibility to reduce the activation of the concrete walls around the reactor vessel to below the free release limit. IRIS is a new integral pressurized water reactor (PWR) developed by an international team led by Westinghouse with an electrical generation capacity of 335 MWe and passive safety systems. Its design differs from larger loop PWRs in that a single building houses the containment as well as all the associated equipment including the control room that must be staffed continuously. The resulting small footprint has positive safety and economic implications, and the integral layout provides additional shielding and thus the opportunity to significantly reduce the activation, but it also leads to significantly more challenging simulations. The difficulty in modeling the entire building is the fact that the source is attenuated over 10 orders of magnitude before ever reaching the accessible areas. For an analog Monte Carlo simulation with no acceleration (variance reduction), it would take many processor-years of computation to generate results that are statistically meaningful. Instead, to generate results for this thesis, the Standardized Computer Analyses for Licensing Evaluation (SCALE) with the package Monaco with Automated Variance Reduction using Importance Calculations (MAVRIC) will be used. This package is a hybrid methodology code where the forward and adjoint deterministic calculations provide variance reduction parameters for the Monte Carlo portion to significantly reduce the computational time. Thus, the first task will be to develop an efficient SCALE/MAVRIC model of the IRIS building. The second task will be to evaluate the dose rate and activation of materials, specifically focusing on activation of concrete walls around the reactor vessel. Finally, results and recommendations will be presented.
This work comprises a radiometric study of Durban‟s solar resource, utilizing data from the Howard College campus of the University of KwaZulu-Natal (UKZN), and the Solar Thermal Applications Research Laboratory (STARlab) at Mangosuthu University of Technology (MUT), located 17 km away. The study has three aims: first to establish a solar radiometric monitoring network for the greater Durban area, comprising the UKZN Howard College and Westville stations, and the STARlab facility at MUT. The UKZN Westville station is under refurbishment and should be operational by the end of 2011. Data from this station are not included in the study. The instrumentation and acquisition software in use at Howard College and STARlab are described. The stations record global horizontal irradiance (GHI), direct normal irradiance (DNI) and diffuse horizontal irradiance (DHI), measured by an unshaded pyranometer, a normal incidence pyrheliometer and a pyranometer shaded with a stationary band respectively. Second, to test a number of existing radiometric models against measured data gathered at the stations. Radiometric models assist in estimating missing components of radiation at stations that do not measure all three components separately, for reasons of cost. The models investigated included Erbs et al. (1982), Orgill and Hollands (1977), Reindl et al. (1990), Boland et al. (2001), and Skartveit and Olseth (1987) and correction models by Drummond et al. (1956), Le Baron et al. (1990), Batlles et al. (1995), and Muneer and Zhang (2000) to correct the shadow band effect. Third, to compare data from the two operational stations and to investigate potential spatial differences in sun strength arising from micro-climate effects in the greater Durban area. This takes the form of a statistical analysis of the differences in radiometric data recorded simultaneously at the UKZN and STARlab stations. The study found that the recorded difference in GHI over one year was 0.72%, which lies within the instrument measurement accuracy. Therefore no measurable radiometric differences due to microclimate could be detected and, for the period in which data were collected, measurements from Howard College could be used to estimate irradiance patterns for MUT, and vice versa. / Thesis (M.Sc.Eng.)-University of KwaZulu-Natal, Durban, 2011.
Determination of natural radioactivity concentrations in soil: a comparative study of Windows and Full Spectrum AnalysisMaphoto, Katse Piet January 2004 (has links)
In this study, two methods of analysing activity concentrations of natural radionuclides (U, Th and K) in soil are critically compared. These are the Window Analysis (WA) and Full Spectrum Analysis (FSA). In the usual WA method, the activity concentrations are determined from the net counts of the windows set around individual &gamma / -ray peaks associated with the decay of U, Th and K. In the FSA method, the full energy spectrum is considered and the measured spectrum is described as the sum of the three standard spectra (associated with U, Th and K, respectively), each multiplied by an unknown concentration. The concentrations are determined from the FSA and correspond to the activity concentrations of U, Th and K in the soil. The standard spectra derived from separate calibration measurements using the HPGe detector, represents the response of the HPGe to a Marinelli sample beaker containing an activity concentration of 1 Bq/kg.
Lic.-avh. Luleå : Luleå tekniska univ., 2005. / Härtill 3 uppsatser.
Desenvolvimento e caracterização de dosímetros para monitoração individual de trabalhadores ocupacionalmente expostos à radiação combinando as técnicas de termoluminescência (TL) e luminescência opticamente estimulada (OSL) / Development and characterization of dosimeters for individual monitoring of workers occupationally exposed to radiation combining the techniques of thermoluminescence (TL) and optically stimulated luminescence (OSL)Malthez, Anna Luiza Metidieri Cruz, 1985- 28 August 2018 (has links)
Orientadores: Vera Lúcia da Silveira Nantes Button, Marcelo Baptista de Freitas / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação / Made available in DSpace on 2018-08-28T09:42:26Z (GMT). No. of bitstreams: 1 Malthez_AnnaLuizaMetidieriCruz_D.pdf: 4070699 bytes, checksum: 5b502eb8b2975aac6052df7ad659d32a (MD5) Previous issue date: 2015 / Resumo: Neste estudo foi desenvolvido um dosímetro (monitor individual) para monitoração externa de indivíduos ocupacionalmente expostos à radiação (raios X e gama) que faz o uso simultâneo das técnicas de termoluminescência (TL) e luminescência opticamente estimulada (OSL - Optically Stimulated Luminescence), combinado às diferentes características dosimétricas de detectores já utilizados com a técnica TL na rotina dos Serviços de Monitoração Individual Externa (SMIEs) no Brasil (LiF:Mg,Ti ¿ TLD100, CaF2:natural, CaSO4:Dy - IPEN) e detectores utilizados com a técnica OSL, ainda pouco explorados na monitoração individual (BeO ¿ Thermalox 995) e recentemente autorizados a serem utilizados com a técnica OSL no país (Al2O3:C - Luxel). Para o desenvolvimento do monitor, diversas características intrínsecas e dosimétricas dos detectores empregando as técnicas TL e OSL em três diferentes equipamentos leitores foram avaliadas. Testes de desempenho foram aplicados ao monitor desenvolvido, conforme critérios estabelecidos no país e no exterior (CASEC e IEC, respectivamente). Os resultados obtidos demonstram que as respostas TL e OSL dos detectores dependem fortemente da configuração do leitor utilizado, da técnica empregada (TL ou OSL) e do tipo de sinal avaliado, no caso da técnica OSL (OSL total ou inicial). Assim é fundamental uma análise prévia de características intrínsecas do material, como comprimento de onda principal da emissão luminescente, tipo (inicial ou total) e magnitude (doses baixa, moderada ou alta) do sinal que será avaliado para a escolha adequada dos parâmetros do leitor (filtros, máscaras, potência, entre outros) empregando as duas técnicas. Os resultados obtidos com a técnica OSL reforçam seu uso na monitoração individual no Brasil, uma vez que estavam em acordo com a técnica TL, amplamente empregada pelos SMIEs nacionais. Além da determinação de dose individual, normalmente empregada na monitoração de trabalhadores, o dosímetro desenvolvido permite também estimar doses acumuladas ao longo do tempo, empregando a técnica OSL nos detectores de Al2O3:C ou BeO, sendo que no caso deste último, a dose única (ou individual) também pode ser determinada com a técnica TL aplicada simultaneamente no mesmo detector. Após a avaliação das respostas em energia dos detectores, um algoritmo foi desenvolvido, testado e validado para avaliar fatores de correção com respeito à energia, baseado na razão entre as respostas de um par de detectores TL e OSL. Os resultados demonstraram que as diferentes razões entre os sinais provenientes do par, permitem avaliar de forma precisa a qualidade da radiação à qual o par de detectores foi exposto. O monitor desenvolvido possui três configurações diferentes de pares de detectores, Al2O3:C/LiF:Mg,Ti, Al2O3:C/BeO e CaSO4:Dy/BeO. Ele apresenta como principais vantagens, em relação aos dosímetros já existentes em uso comercialmente, a possibilidade de poder inferir informações sobre a dose e qualidade da radiação (energia efetiva) sem a utilização de filtros e com diminuição das incertezas associadas, avaliar doses acumuladas ao longo do tempo com o mesmo dosímetro e combinar todas as características dos detectores associadas às técnicas TL e OSL, simultaneamente em um mesmo dosímetro. Os resultados dos testes de desempenho do monitor apresentaram conformidade com os critérios nacionais e internacionais estabelecidos, e contribuíram para que os critérios nacionais utilizados para a técnica TL possam ser estendidos para a técnica OSL / Abstract: In this study a dosimeter (personal monitor) for external monitoring of individuals occupationally exposed to radiation (X and gamma rays) was developed using simultaneously thermoluminescent (TL) and optically stimulated luminescence (OSL) techniques. Intrinsic characteristics of detectors already used with TL technique in External Individual Monitoring Services routine in Brazil (LiF:Mg,Ti ¿ TLD 100, CaF2:natural and CaSO4:Dy ¿ IPEN) were combined to detectors used with OSL technique, one less explored (BeO ¿ Thermalox 995), and other recently approved (Al2O3:C - Luxel) to be used in individual monitoring in the country (Al2O3:C - Luxel). During the monitor development, several intrinsic and dosimetric characteristics of detectors were evaluated employing TL and OSL techniques in three different reader equipments. Performance tests were applied to the developed monitor according to national and international established criteria (CASEC and IEC, respectively). The obtained results showed that the responses of TL and OSL detectors are strongly dependent on reader configuration, employed technique (TL and OSL) and, in the particular case of OSL technique, also the signal (total or initial OSL). Therefore, a previous analysis of the intrinsic characteristics of the material, as the main wavelength of the luminescent emission, the signal type (initial or total) and dose magnitude (low, moderate or high) must to be made in order to select the reader configuration (filters, power, and others) used with each technique. The results obtained with OSL technique reinforce its use in Brazil, as they were in agreement with TL technique, which is already largely used by national EIMS. In addition to the assess of individual dose, usually employed in workers monitoring, the developed dosimeter allows evaluating accumulated dose over time using OSL technique with Al2O3:C or BeO detectors, and single or individual doses can be evaluated applying TL technique simultaneously applied in the same detector. After the evaluation of the energy response of detectors, an algorithm was developed, tested and validated to assess correction factors with respect to energy, based on the ratio of the responses of a pair of TL and OSL detectors. The results confirm that the different ratios between signals from a detector pair allow to evaluate more accurately the radiation quality to that the pair of detectors were exposed. The monitor was developed with three different arrangements of pairs of detectors, Al2O3:C/LiF:Mg,Ti, Al2O3:C/BeO and CaSO4:Dy/BeO. It presents as main advantages, compared to existing commercial dosimeters in use, the possibility to infer information on the dosage and quality of radiation (effective energy) without the use of filters and reducing associated uncertainties, to assess cumulative doses over time with the same dosimeter, and to combine all features of the detectors associated with TL and OSL techniques, simultaneously, in the same dosimeter. The results of the performance tests of the developed monitor were in accordance to national and international criteria, and contributed to that the national criteria, used for TL technique, can also be extended to the OSL technique / Doutorado / Engenharia Biomedica / Doutora em Engenharia Elétrica
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