3,042 research outputs found
Pharmacokinetic behavior of Rituximab: a study of different schedules of administration for heterogeneous clinical settings.
No full textThis study was designed to report the pharmacokinetic
behavior of Rituximab in patients affected with different diseases
and treated with different schedules of administration. A low tumor
burden was a common feature of all patients (N = 48) included in our
study, whereas the timing of Rituximab administration varied from
weekly (groups 1, 2, 3) to monthly (group 4). Group 1 included patients
with follicular lymphoma treated with 4 weekly doses of
Rituximab after first-line chemotherapy with CHOP. At the start of
Rituximab, patients were in partial or complete clinical response but
showed persistence of disease at molecular level (bcl-2–positive) in
bone marrow and/or peripheral blood. Patients in group 2 had autoimmune
disorders and Rituximab was given to act on B-cells, interfering
with their production of autoantibodies. In patients with amyloidosis
(group 3), Rituximab was given to kill progenitor B-cells of the small
clone terminating in amyloid-producing plasma cells. In groups 2 and
3, the target of monoclonal antibody was a population of small B
cells, which make an intrinsic feature of the diseases. Group 4 included
patients with relapsed or refractory follicular and mantle cell
lymphoma who underwent a salvage program of immunochemotherapy,
purging in vivo and autotransplant: the first of the six planned
doses of Rituximab was administered after a debulking phase with a
third-generation regimen, such as VACOP-B. An enzyme-linked immunoassay
(ELISA) developed and validated in our laboratory was
used for the pharmacokinetic study. Rituximab disposition was characterized
by a 2-exponential decay, with a long elimination half-life
of approximately 3 weeks (range, 248–859 hours). The total systemic
clearance ranged between 3.1 and 11.9 mL/hr/m2. After 4 weekly infusions,
Rituximab concentration was ;2.5 mg/mL, which is approximately
85% of the steady-state level. Steady-state plasma concentrations
of Rituximab were reached after 6 to 8 weekly infusions. The adopted
pharmacokinetic model (2-compartment open model) seems to provide
the best fit of Rituximab disposition both during and after treatment,
even when different schedules of drug administration are used. Because
several studies reported an association between response and
serum Rituximab concentrations, a treatment based on a pharmacokinetic
model may be useful for predicting the desired drug
concentration
Pharmacokinetic Behavior of Rituximab: A Study of Different Schedules of Administration for Heterogeneous Clinical Settings
No full textThis study was designed to report the pharmacokinetic behavior of Rituximab in patients affected with different diseases and treated with different schedules of administration. A low tumor burden was a common feature of all patients (N=48) included in our study, whereas the timing of Rituximab administration varied from weekly (groups 1, 2, 3) to monthly (group 4). Group 1 included patients with follicular lymphoma treated with 4 weekly doses of Rituximab after first-line chemotherapy with CHOP. At the start of Rituximab, patients were in partial or complete clinical response but showed persistence of disease at molecular level (bcl-2-positive) in bone marrow and/or peripheral blood. Patients in group 2 had autoimmune disorders and Rituximab was given to act on B-cells, interfering with their production of autoantibodies. In patients with amyloidosis (group 3), Rituximab was given to kill progenitor B-cells of the small clone terminating in amyloid-producing plasma cells. In groups 2 and 3, the target of monoclonal antibody was a population of small B cells, which make an intrinsic feature of the diseases. Group 4 included patients with relapsed or refractory follicular and mantle cell lymphoma who underwent a salvage program of immunochemotherapy, purging in vivo and autotransplant: the first of the six planned doses of Rituximab was administered after a debulking phase with a third-generation regimen, such as VACOP-B. An enzyme-linked immunoassay (ELISA) developed and validated in our laboratory was used for the pharmacokinetic study. Rituximab disposition was characterized by a 2-exponential decay, with a long elimination half-life of approximately 3 weeks (range, 248-859 hours). The total systemic clearance ranged between 3.1 and 11.9 mL/hr/m. After 4 weekly infusions, Rituximab concentration was approximately 2.5 microg/mL, which is approximately 85% of the steady-state level. Steady-state plasma concentrations of Rituximab were reached after 6 to 8 weekly infusions. The adopted pharmacokinetic model (2-compartment open model) seems to provide the best fit of Rituximab disposition both during and after treatment, even when different schedules of drug administration are used. Because several studies reported an association between response and serum Rituximab concentrations, a treatment based on a pharmacokinetic model may be useful for predicting the desired drug concentration
A new sensitive enzyme-linked immunosorbent assay (ELISA) for Alemtuzumab determination: development, validation and application
No full textAlemtuzumab is a humanized (IgG(1)) rat monoclonal antibody to CD52 antigen and is currently used in the treatment of chronic lymphocytic leukemia (CLL) and other CD52-positive lymphoproliferative disorders. Various techniques have been developed to measure Alemtuzumab levels in human serum/plasma. The authors report on the validation of a very sensitive enzyme-linked immunosorbent assay (ELISA) to measure serum concentrations of the humanized IgG(1) using a rabbit polyclonal antibody specifically produced against the rat sequence of Alemtuzumab after papain digestion. The assay was successfully applied to test the serum samples of patients with B-lymphocyte CLL who received Alemtuzumab subcutaneously. This ELISA assay could be easily used to determine human serum levels of Alemtuzumab pre- and post-treatment to optimize dosing and scheduling and to study the relationship between dose and clinical response
Receiver Windowing Design for Narrowband Interference Mitigation in MB-OFDM UWB System
No full textIn 2005, the WiMedia Alliance working with the European Computer Manufacturers Association (ECMA) announced the establishment of the WiMedia MB-OFDM (Multiband Orthogonal Frequency Division Multiplexing) UWB radio platform as their global UWB standard. It was also chosen as the physical layer (PHY) of high data rate wireless specifications for high speed Wireless USB (W-USB), Bluetooth 3.0 and Wireless High-Definition Media Interface (HDMI). However, due to the low power and wide bandwidth nature of UWB systems, in-band narrowband interference (NBI) may hinder the receiver performance. This thesis presents an analysis of NBI impact on the MB-OFDM system for UWB communication. The intent of our analysis is to provide practical solutions for interference mitigation under different NBI models. In our work, a new receiver windowing for zero padding (ZP) OFDM system is proposed to reduce NBI spreading in the MB-OFDM UWB system. Simulations demonstrate the effectiveness of windowing under different NBI models.Microelectronics & Computer EngineeringElectrical Engineering, Mathematics and Computer Scienc
Altered immunolocalization of FGF23 in murine femora metastasized with human breast carcinoma MDA-MB-231 cells
No full textIntroduction After the onset of bone metastasis, tumor cells appear to modify surrounding microenvironments for their benefit, and particularly, the levels of circulating fibroblast growth factor (FGF) 23 in patients with tumors have been highlighted. Materials and methods We have attempted to verify if human breast carcinoma MDA-MB-231 cells metastasized in the long bone of nu/nu mice would synthesize FGF23. Serum concentrations of calcium, phosphate (Pi) and FGF23 were measured in control nu/nu mice, bone-metastasized mice, and mice with mammary gland injected with MDA-MB-231 cells mimicking primary mammary tumors. Results and conclusions MDA-MB-231 cells revealed intense FGF23 reactivity in metastasized lesions, whereas MDA-MB-231 cells cultured in vitro or when injected into the mammary glands (without bone metastasis) showed weak FGF23 immunoreactivity. Although the bone-metastasized MDA-MB-231 cells abundantly synthesized FGF23, osteocytes adjacent to the FGF23-immunopositive tumors, unlike intact osteocytes, showed no FGF23. Despite significantly elevated serum FGF23 levels in bone-metastasized mice, there was no significant decrease in the serum Pi concentration when compared with the intact mice and mice with a mass of MDA-MB-231 cells in mammary glands. The metastasized femora showed increased expression and FGFR1 immunoreactivity in fibroblastic stromal cells, whereas femora of control mice showed no obvious FGFR1 immunoreactivity. Taken together, it seems likely that MDA-MB-231 cells synthesize FGF23 when metastasized to a bone, and thus affect FGFR1-positive stromal cells in the metastasized tumor nest in a paracrine manner
ASIC FFT processor for MB-OFDM UWB system
No full textThe physical layer (PHY) standard of Multi-band Orthogonal Frequency Division Multiplexing (MB-OFDM) Ultra Wideband (UWB) system was defined by ECMA International. In this standard, the data sampling rate from the analog-to-digital converter to the physical layer is up to 528 Msample/s. Therefore, it is a challenge to realize the physical layer of the UWB system-especially the components with high computational complexity in Very Large Scale Integration (VLSI) implementation. Fast Fourier Transform (FFT) block is one of these components. FFT plays an important role in Multi-band OFDM UWB system, which is the demodulation block of OFDM signals. The purpose of this project is to design an Application Specific Integrated Circuit (ASIC) FFT solution for this system. The specification is defined from the system analysis and literature research. All the design choices and considerations are concluded and explained.Based on the algorithm and architecture analysis, a novel Radix22Parallel processor is proposed, which is a small-area and low-power-consumption solution for MB-OFDM UWB system. Both Field Programmable Gate Array (FPGA) and ASIC targeted synthesis results of this architecture are presented.Electrical Engineering, Mathematics and Computer Scienc
Rituximab (IDEC-C2B8): validation of a sensitive enzyme-linked immunoassay applied to a clinical pharmacokinetic study
No full textRituximab is a chimeric monoclonal antibody (MAb) directed against the B-cell CD20 antigen that has been approved for therapy of relapsed and resistant follicular. non-Hodgkin's lymphoma (NHL). This study describes the development and validation of a highly sensitive, rapid, accurate, precise enzyme-linked immunosorbent assay (ELISA) to measure Rituximab serum concentrations. This study also describes the application of the ELISA method to a pharmacokinetic study in a homogeneous group of patients with follicular lymphoma who received 4 weekly doses of MAb at the standard dose of 375 mg/m(2) as consolidation of chemotherapy. In the patients in this study, the median Rituximab serum concentrations increased during therapy, and showed a slow decline during the posttreatment period. The Rituximab elimination half-life of approximately 20 days accounts for the demonstrated accumulation of MAb in serum samples. Because previous pharmacokinetic studies showed a correlation between Rituximab serum levels and tumor response, the ELISA method used in this study, which allows a precise control of serum concentrations, could be useful for predicting the final response to the MAb and for selecting patients able to benefit from higher dosage or repeated drug administration
Characterization of the tertiary structure of the de novo designed protein MB-1
No full textMilk Bundle-1 (MB-1) is a de novo designed protein with 100 amino acids, having a molecular weight of 11.4 kilodaltons. MB-1 is enriched with 57% of selected essential amino acids (methionine, threonine, lysine and leucine), which are known to be limiting in dairy cattle. Recently, on the basis of a digestibility study, MB-1 was predicted to be unstable in rumen conditions.Characterization of the protein's structure was achieved using fluorescence spectroscopy (steady state measurements). MB-1 contains one tyrosine at position 62, expected to be in position "d" of helix III, in the hydrophobic core. Data obtained using fluorescence quenching indicates that the tyrosine is protected from the solvent in the putative hydrophobic core, as per design.Once it was established that MB-1 was not misfolded, further experiments were done to assess the fluidity of its hydrophobic core. For this, the amphiphillic dye ANSA was used. Results obtained for MB-1 compare favourably to those of many natural proteins, suggesting that MB-1 has achieved some degree of nativeness. Interestingly, MB-1 was found to exclude ANSA from its hydrophobic core more efficiently than all other de novo designed proteins reported to date.Finally, an analysis of folding thermodynamics of MB-1 was attempted. It was found that the fluorescence intensity of tyrosine was not sensitive to unfolding, making thermodynamic data impossible to obtain.Analysis of the data on MB-1 as compared to other natural proteins indicates that MB-1 is folded and compact. The lack of resistance to proteases must be caused by other factors other than the lack of compactness or misfolding. (Abstract shortened by UMI.).Source: Masters Abstracts International, Volume: 36-06, page: 1623.Adviser: Marc Beauregard
Stochastic Lie bracket (derivation, derivation) in MB-algebras
No full textBy a stochastic controller, we make stable the pseudo stochastic Lie bracket (derivation, derivation) in complex MB-algebras. Next, we get an approximation by a stochastic Lie bracket (derivation, derivation) and calculate the maximum error of the estimate. © 2020, The Author(s)
Weerkat: An extensible semantic Wiki
No full textWikis are Web applications that blur the boundaries between readers and authors, allowing non-technical people to author hypertexts through a web interface. A Semantic Wiki is a Wiki that attempts the same thing with the Semantic Web, allowing non-technical users to create semantic resources and/or ontologies. In this paper we characterise the different ways in which a Wiki might support the Semantic Web and present Weerkat, a modular and extensible Wiki that has ontological hypertext support. Key to this has been the design and development of a highly flexible Wiki architecture which allows easy modification and augmentation of functionality
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