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Biomedical subjects

M Kirk

Publications and source records attributed to M Kirk.

103 records · Page 6Linked to original sources
PubMedDate not supplied

Further studies on the protein conjugation of hydroxamic acid bifunctional chelating agents: group-specific conjugation at two different loci.

A procedure utilizing an activated ester approach for conjugation of unprotected hydroxamic acids to antibodies and peptides was recently reported. Here, an alternative method with advantages over the activated ester strategy is described. This protocol utilizes the hydrazone formation between a hydrazide derivative of the trihydroxamate ligand trisuccin and either a ketone derivative of antibody or the aldehyde groups, generated by oxidation of the carbohydrate residues. Thus, the trisuccin carboxylic acid (1) was derivatized with tert-butyl carbazate to the hydrazide 2, and the protecting groups were removed by catalytic hydrogenation and acidolysis with TFA to afford the hydroxamate hydrazide 4. Conjugation of 4 to monoclonal antibody CC49 was effected by two approaches: attachment through the amine (e.g., lysine) residues of the antibody or oxidation of the carbohydrate residues. The extent of conjugations were monitored by MALDI, through evaluation of the increases in molecular weights of the conjugates compared to the unconjugated antibody. The first approach utilizing a ketone linker (6-oxoheptanoic acid, OHA) which served as a hydrazide anchor, is being introduced in this report as a new technique for conjugation of hydrazide derivatives to proteins. The OHA approach proved to be a superior strategy over the aldehyde approach in the ease of the procedure and yield of protein recovery. It also had the advantage of yielding more control in adjusting the ligand-to-protein ratio and was therefore selected for protocol optimization. All conjugates resulting from both approaches were radiolabeled with 125I and screened for their immunoreactivity. Furthermore, the conjugates prepared through the optimized OHA protocol were radiolabeled with both 99mTc and 125I for which the radiolabeling yields and immunoreactivities are reported.

Antibodies, Monoclonal↗
PubMedDate not supplied

Differential activity of maternally and paternally derived chromosome regions in mice.

Although both parental sexes contribute equivalent genetic information to the zygote, in mammals this information is not necessarily functionally equivalent. Diploid parthenotes possessing two maternal genomes are generally inviable, embryos possessing two paternal genomes in man may form hydatidiform moles, and nuclear transplantation experiments in mice have shown that both parental genomes are necessary for complete embryogenesis. Not all of the genome is involved in these parental effects, however, because zygotes with maternal or paternal disomy for chromosomes 1, 4, 5, 9, 13, 14 and 15 of the mouse survive normally. On the other hand, only the maternal X chromosome is active in mouse extraembryonic membranes, maternal disomy 6 is lethal, while non-complementation of maternal duplication/paternal deficiency or its reciprocal for regions of chromosome 2, 8 and 17 has been recognized. We report that animals with maternal duplication/paternal deficiency and its reciprocal for each of two particular chromosome regions show anomalous phenotypes which depart from normal in opposite directions, suggesting a differential functioning of gene loci within these regions. A further example of non-complementation lethality is also reported.

Animals↗
PubMedDate not supplied

Commercial gene testing: the need for professional and public debate.

Commercial gene tests are currently available in the UK and the range of tests offered is likely to increase. While knowing their genetic status may bring benefits to individuals and their families, genetic testing also brings its own unique problems. Commercial ventures may do little to resolve these and adequate safeguards are needed to ensure that clients undergoing testing are not disadvantaged. The availability of gene tests can only serve to heighten public awareness of the relevance of genetics to health care, and there is likely to be an increased demand for information and advice from healthcare professionals before, and following, testing. Nurses should be prepared to acquire adequate knowledge to maintain their role as health educators, and to participate in public and professional debate on the issues that commercial testing highlights.

Genetic Counseling↗
PubMedDate not supplied

Relative concerns associated with genetics and surrogacy.

Assisted reproductive technologies, incorporating artificial insemination and in-vitro fertilization techniques, are widely practised across Europe. Concern about surrogacy prompted the UK Government to commission a review and consultation on surrogacy arrangements. The ensuing document was concerned primarily with the questions of payment to the surrogate, and the regulation of agencies involved in surrogacy arrangements. This author feels that more fundamental issues should first be debated by both health professionals and society. Genetic aspects of surrogacy merit special attention, particularly regarding the genetic contribution to parenthood and the ownership and use of genetic information. Health professionals need to be fully aware of the ethical implications of advances in genetics and technology when they are applied to assisted reproduction.

Female↗