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Immunoassay of thyroxineMpoko, C. N. January 1985 (has links)
No description available.
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Methotrexate-polymer conjugatesDellow, Jan L. January 1991 (has links)
No description available.
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Ferrocene conjugates as potential anticancer agentsDago N’Da, David 10 February 2006 (has links)
PhD - Science / Methotrexate (MTX) is a highly potent drug against leukemia and other neoplasias. The drug is notorious, however, for exerting toxic side effects and inducing drug resistance in the target cells as a result of deficiencies in the active carrier-mediated membrane-crossing mechanism. The bioreversible binding to a
water-soluble and biocompatible carrier polymer is an advanced technology designed to circumvent critical pharmacological hurdles the drug must clear for efficacious biological action.
The present project aimed at the anchoring of MTX and other drugs to various primary amine-functionalized polymeric carriers and the evaluation of the cytotoxic performance of the resulting conjugates in cell culture tests.
The polymeric carriers used were polyaspartamides, prepared by an aminolytic
ring-opening process of polysuccinimide, and poly(amidoamines), on the other hand, obtained by the copolymerization of methylenebisacrylamide with mono-N- tert-butoxycarbonyl-protected primary diamine and bifunctional amines.
The anchoring was achieved through formation of biofissionable amide bonds. The in vitro biological evaluation against various human cell lines revealed the polymer-MTX conjugates to be more active than the clinically used parent drug.
In order to demonstrate the multidrug-binding capacity of the polyaspartamidetype carriers, and at the same time ensuring target-specific drug delivery, folic acid, a potential cell entry facilitator, was co-conjugated to selected polymeric conjugates containing MTX or ferrocene.
The in vitro inhibition of cell growth by the folate-drug co-conjugates was also evaluated against the same human cell lines.
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Production of variants of mitogillin with reduced IgE binding activityNg, Wai-yun, Louisa. January 2004 (has links)
Thesis (M. Med. Sc.)--University of Hong Kong, 2004. / Also available in print.
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Construction of a Recombinant ImmunotoxinJanuary 1995 (has links)
In recent years a number of therapeutically useful immunotoxins have been produced using recombinant gene technology. In general, this involves fusion of a toxin gene with sequence encoding a variety of clinically relevant proteins or peptides. Using these techniques a recombinant immunotoxin has been engineered by fusing the genes encoding an antibody fragment with the sequence of a small cytolytic peptide, melittin. The antibody fragment consists of the antigen binding site derived from a murine monoclonal antibody K- 1-21, which binds to human free kappa light chains and recognises a specific epitope (KMA) expressed on the surface of human myeloma and lymphoma cells. The toxic portion of the molecule is melittin, a 26 amino acid, membrane lytic peptide which is a major component of bee venom. Using PCR a single chain Fv (scFv) was constructed by linking VH and VL genes with an oligonucleotide encoding a flexible, hydrophilic peptide. The melittin gene was synthesised as an oligonucleotide and extended by PCR. Nucleotide sequence encoding a linker peptide was added to the 5' end and a primer encoding a FLAG peptide was used to extend the 3' end. This gene construct was then ligated into the recombinant expression vector, pPOW scFv, to create the fusion gene encoding the recombinant immunotoxin. The gene construct was expressed in the periplasm of E.coli (TOPP2) using the secretion signal pelB . Expression of the foreign protein was monitored by western blot using a monoclonal antibody which recognises the FLAG peptide encoded at the carboxy terminal region of the gene construct. Expression of the recombinant immunotoxin was optimised and the resulting protein was purified using anti-FLAG M2 affinity chromatography. Antigen binding activity was assessed by ELISA and flow cytometry using a human myeloma cell line, HMy2, which expresses the KMA antigen.Binding of the immunotoxin to a control human cell line, K562, which does not express KMA on the cell surface was also assessed. The results indicated that the recombinant immunotoxin retained antigen binding specificity and it was cytotoxic towards the target cell line (HMy2).
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Simple and Rapid Quantitation of 21 Bile Acids in Rat Serum and Liver by UPLC-MS-MS: Effect of High Fat Diet on Glycine Conjugates of Rat Bile AcidsISHII, AKIRA, SENO, HIROSHI, HATTORI, HIDEKI, OGAWA, TADASHI, NAKAJIMA, TAMIE, KITAMORI, KAZUYA, NAITO, HISAO, NOMURA, MINA, KANEKO, RINA, SUZUKI, YUDAI 02 1900 (has links)
No description available.
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Construction of a Recombinant ImmunotoxinJanuary 1995 (has links)
In recent years a number of therapeutically useful immunotoxins have been produced using recombinant gene technology. In general, this involves fusion of a toxin gene with sequence encoding a variety of clinically relevant proteins or peptides. Using these techniques a recombinant immunotoxin has been engineered by fusing the genes encoding an antibody fragment with the sequence of a small cytolytic peptide, melittin. The antibody fragment consists of the antigen binding site derived from a murine monoclonal antibody K- 1-21, which binds to human free kappa light chains and recognises a specific epitope (KMA) expressed on the surface of human myeloma and lymphoma cells. The toxic portion of the molecule is melittin, a 26 amino acid, membrane lytic peptide which is a major component of bee venom. Using PCR a single chain Fv (scFv) was constructed by linking VH and VL genes with an oligonucleotide encoding a flexible, hydrophilic peptide. The melittin gene was synthesised as an oligonucleotide and extended by PCR. Nucleotide sequence encoding a linker peptide was added to the 5' end and a primer encoding a FLAG peptide was used to extend the 3' end. This gene construct was then ligated into the recombinant expression vector, pPOW scFv, to create the fusion gene encoding the recombinant immunotoxin. The gene construct was expressed in the periplasm of E.coli (TOPP2) using the secretion signal pelB . Expression of the foreign protein was monitored by western blot using a monoclonal antibody which recognises the FLAG peptide encoded at the carboxy terminal region of the gene construct. Expression of the recombinant immunotoxin was optimised and the resulting protein was purified using anti-FLAG M2 affinity chromatography. Antigen binding activity was assessed by ELISA and flow cytometry using a human myeloma cell line, HMy2, which expresses the KMA antigen.Binding of the immunotoxin to a control human cell line, K562, which does not express KMA on the cell surface was also assessed. The results indicated that the recombinant immunotoxin retained antigen binding specificity and it was cytotoxic towards the target cell line (HMy2).
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Factors that influence tumour targeting by the enhanced permeability and retention (EPR) effectSat, Nee Yee January 1999 (has links)
No description available.
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The Synthesis and Characterization of Carborane and Metallocarborane-Carbohydrate ConjugatesGreen, Andrew 04 1900 (has links)
<p> This thesis describes the synthesis and characterization of a series of carborane
and metallocarborane-carbohydrate conjugates as model systems for developing a novel
class of radiophannaceuticals. The role of the carborane group is to provide a site for
binding radioactive elements while the carbohydrate moieties are present either as a
targeting vector, or as a means by which to increase the hydrophilicity of the overall
complex. In this research, the versatility of carboranes was demonstrated since it was
shown that carbohydrate-nido-carborane derivatives could be labeled with both metals
(Re/99Tc) and halogens (125I/127I). </p> <p> The initial synthetic target was compound 2.6, a simple nido-carboranyl glycoside
of glucose. The syntheses of this model ligand and its Re-metallocarborane (2.1, 3.4) and
iodinated (2.13) derivatives were carried out in order to determine the optimal methods
and conditions for synthesis and purification of bifunctional ligands and the
corresponding radioactive analogues. Microwave irradiation was found to greatly
enhance the synthesis ofRe and 99mTc-metallocarborane complexes which were isolated
in 31% and 58% yield respectively. Analysis of the Re complexes by 1H nOe NMR
spectroscopy revealed that rearrangement of the carborane cage from the expected 3,1 ,2-
ReC2B9 isomer to the 2,1 ,8- isomer occurred under the synthetic conditions employed. </p> <p> Iodination and radioiodination of model compound 2.6 was carried out using
Na[1271] or Na[125I] in the presence of Chloramine-T or Iodogen as oxidants at room
temperature. Reactions were complete in 5 min and the products isolated in 21% and
29% yield for 127I and 125I, respectively. </p> <p> Building on these results, bifunctional compounds 4.3 and 4.12 were prepared.
Using microwave heating, these compounds were labeled with 99mTc in 62% and 44%
yield, respectively. Compounds 4.3 and 4.12 contained a benzoic acid functionality
through which conjugation to targeting vectors could be accomplished. To demonstrate
this, benzamides 4.14 and 4.16 were synthesized using an active ester approach. The
products were isolated in 41% and 35% yield and subsequently labeled with 1251 using the
methods developed for the model system. Compounds [1251]-4.23 and [1251]-4.24 were
obtained in 73% and 92% yield, respectively. The stability of these [1251]-labeled
compounds was excellent, showing less than 1% degradation after 24 hours in solution.
In order to assess the effect of the carbohydrate moiety upon lipophilicity, the log P of the
radiolabeled benzamides was measured and found to be 1.53±0.01 for [125I]-4.23 and
0.82±0.04 for [1251]-4.24. This result confirmed the increase in hydrophilicity associated
with the presence of the carbohydrate moiety. </p> <p> Progress was also made towards preparing a glucose-nido-carborane conjugate
(5.9) whose Re and Tc complexes were pursued as metallocarborane analogues of the
clinical PET tracer [18F]FDG. The key precursor was made in good overall yield and the
product fully characterized. Future work should focus on preparing the radiolabeled
analogues. </p> / Thesis / Doctor of Philosophy (PhD)
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The cutaneous disposition of the sensitizing chemicals hydroxycitronellal and dinitrochlorobenzeneTonge, Robert Patrick January 1995 (has links)
No description available.
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