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Biomedical subjects

R Moseley

Publications and source records attributed to R Moseley.

At least 37 records · Page 2Linked to original sources
PubMed1997

Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes.

The effect of reactive oxygen species (ROS), generated by in vitro stimulation of isolated PMN upon the main GAG components of mineralised and non-mineralised connective tissues was investigated. PMN were isolated from whole blood and the production of the ROS superoxide (O2.-) and hydroxyl radicals (.OH) was stimulated by the addition of phorbol myristyl acetate (PMA) and PMA/FeCl3-EDTA chelate respectively and their production assessed over a 24 h period. The glycosaminoglycans (GAG), hyaluronan, chondroitin 4-sulphate and dermatan sulphate, were exposed to the ROS fluxes, incubated at 37 degrees C for 1 h and 24 h. GAG fragmentation was examined by gel exclusion chromatography and modification to hexuronic acid and hexosamine residues determined. Stimulation of PMN with PMA resulted in a burst of O2.- production for 1 h, which was sustained at a reduced level for 24 h. Fragmentation of GAG was observed for all GAG examined. Modification to the GAG was evident, with hyaluronan being more susceptible to loss of GAG residues than sulphated GAG. Modification of sugar residues increased with the incubation time and loss of the hexuronic acid residues was greater than loss of hexosamine residues. Addition of FeCl3-EDTA chelate, which led to the generation of .OH and was sustained over the 24 h period, demonstrated similar trends of GAG modification although increased degradation and loss of hexosamine and hexuronic acid were observed. GAG chains are constituents of PGs and their modification is likely to affect the function of these macromolecules and be of importance in considering the pathogenesis of inflammatory diseases, including periodontal diseases.

Glycosaminoglycans↗
PubMed1996

Influence of titanium oxide and titanium peroxy gel on the breakdown of hyaluronan by reactive oxygen species.

The molecular events occurring at the interface between titanium and connective tissue were investigated in order to help explain the unique biocompatible properties of titanium implants and their successful osseointegration into bone tissue. In this study the influence of commercially pure titanium and titanium peroxy gels on the breakdown of the connective tissue component and serum derived factor, hyaluronan, by reactive oxygen species (ROS), produced during the insertion of an implant in vivo, was examined. Hyaluronan breakdown was monitored in vitro in the presence of a hydroxyl radical flux, generated in the presence and absence of titanium powder and discs. Parallel studies examined the breakdown of hyaluronan by hydroxyl radicals in the presence of a titanium peroxy gel, prepared by incubation of the titanium powder or discs in concentrated hydrogen peroxide. The hyaluronan degradation products were separated according to their hydrodynamic size by gel exclusion chromatography. Similarly, experiments were also performed examining the degradation of 2-deoxy-D-ribose by a hydroxyl radical flux in order to demonstrate the detrimental potential of the hydroxyl radicals and to provide a measure of the effectiveness of titanium and titanium peroxy gels as scavengers of ROS. Titanium reduced the harmful effects of the hydroxyl radicals on the breakdown of hyaluronan, presumably acting as a scavenger for the reactive species, possibly by absorbing them into its surface oxide layer, which spontaneously forms on the surface. In contrast, the formation of a titanium peroxy gel from the titanium powder or on the surface of titanium discs enhanced breakdown of both the hyaluronan chains and 2-deoxy-D-ribose. The implications of these findings with regards to the biocompatible nature of the titanium and the ability of these implants to successfully osseointegrate are discussed.

Biocompatible Materials↗
PubMed1995

The chemical modification of glycosaminoglycan structure by oxygen-derived species in vitro.

The effect of reactive oxygen species (ROS) on the chemical structure of glycosaminoglycans (GAG) was studied in order to consider their role in connective tissue damage during an inflammatory disease state such as periodontal disease. GAG were exposed to a radical generating system for 1 h and analysed by gel filtration for fragmentation and chemically with respect to uronic acid, hexosamine and sulfate content. Non-sulfated GAG, hyaluronan and chondroitin, were most susceptible to depolymerisation and chemical modification of uronic acid and hexosamine residues by ROS. Depolymerisation and chemical modification of sulfated GAG, chondroitin 4-sulfate, dermatan sulfate and heparan sulfate was significantly less than for non-sulfated GAG. The highly sulfated GAG heparin showed minimal depolymerisation by ROS, but uronic acid residues were readily modified. Analysis of the ROS-exposed residues suggests that uronic acid is capable of degrading to a 3-carbon aldehyde, malondialdehyde. Chondroitin sulfate exposed to ROS resulted in marginal desulfation. The results suggest that the presence of sulfate on the GAG chain may protect the molecule against ROS attack. However, chemical modification of GAG may affect proteoglycan function and be of importance in considering connective tissue destruction in a variety of pathological situations, including periodontal disease.

Chondroitin Sulfates↗
PubMed1993

Ethical and practical implications of the human genome initiative for family medicine.

Major advances in predictive genetic testing resulting from the Human Genome Initiative could change significantly the routine practice of family medicine. Family physicians should be aware that increased genetic information may affect patients' abilities to acquire and maintain insurance and employment and that interested parties will have incentives to seek this information. The social consequences of genetic information, as well as increased health promotion efforts, may raise problems of informed consent and confidentiality. In addition to their ethical implications, these developments will also affect the practice of family physicians in practical ways such as record keeping. We discuss cases that illustrate the potential impact of these emerging technologies on the practice of family medicine.

Adult↗
PubMed1991

Commentary: maintaining the somatic/germ-line distinction: some ethical drawbacks.

Determinations of the ethical acceptability of genetic therapy have relied on several distinctions in attempts to separate ethically acceptable genetic therapy from those possible therapies that could lead to genetic modifications of future human beings. One distinction that has been proposed is that genetic modifications of human somatic cells is ethically acceptable but that germ-line genetics modifications would be ethically objectionable. This paper examines several serious difficulties which call into question the ethical relevance of a somatic/germ-line distinction.

Double Effect Principle↗
PubMed1989

Monoclonal antibodies M340 and UJ181.4 recognize antigens associated with primitive neuroectodermal tumours/tissues.

Monoclonal antibodies UJ181.4 and M340 were raised from separate fusions using either human foetal brain or medulloblastoma tissue as immunogens. The antibodies are both of IgG isotype and bind to their target antigens with affinities in excess of 10(-9) M. Both monoclonal antibodies have been shown to bind to primitive neuroectodermal tumours and human foetal brain. Expression of the two antigens is developmentally regulated as no binding is detected on adult brain as determined by a variety of indirect binding assays. The two monoclonal antibodies can be clearly distinguished by their migration in a pH gradient (isoelectric focussing gels). UJ181.4 and M340 clearly recognize two different epitopes, as it is not possible to block the binding of one antibody with an excess of the other. In addition, careful study of the binding profiles of the two reagents suggest that they recognize two distinct antigens, although these have not been biochemically characterized. The reagents have proved particularly useful in both the differential diagnosis of the small round cell tumours of childhood and anaplastic brain tumours. In addition, they have formed part of a panel of reagents used for the immunomagnetic depletion of neuroblasts from bone marrow and have been used for targeting radionuclides to tumour cells in the intrathecal compartment.

Animals↗
PubMed1986

Advance directives in family practice.

Advance directives have emerged in medicine as an important method by which patients can express future treatment wishes. The major reasons medical professionals have been reluctant to use advance directives are not because of theoretical defects with advance directives, but because of procedural difficulties. Confusion over types of advance directives and their legal status will ease with increased knowledge of advance directives by health professionals. Additionally, that they are often formulated in ambiguous terms and under situations where the patient's competence is in question can be minimized. More widespread and effective use of advance directives will occur if the family physician takes an active role in identifying patients for whom an advance directive would be desirable, effectively communicating information about advance directives, advising their patients about the most effective way to state their directive in medically precise terminology, and explaining when necessary the patient's wishes to other medical specialists and family members.

Decision Making↗
PubMed1976

Ethical issues arising from human genetics.

Advances in understanding genetic disorders have been rapid in the last few years and with them the need and desire for genetic counselling have grown. Almost simultaneously, particularly in the USA, several large screening programmes have been initiated to screen large numbers of people who may be carriers of such deleterious genes as those of Tay-Sachs disease and sickle cell anaemia. The authors of this paper, clinical medical students at University College Hospital, London, spent some time studying the ethical issues raised. The first part of their study, which is not published here, relates to the biochemistry of certain genetic disorders, so leading up to the aspect of the subject which must concern readers of this journal, genetic counselling. At present genetic counselling is generally the province of the medical practitioner working with clinical biochemists, and in this paper their function is described and how programmes of screening for carriers are designed. Whether the subjects of the screening tests are found to be 'innocent' or 'guilty' psychological problems confront them, and of these the genetic counsellor must be aware. In fact the range of ethical problems raised by such counselling is wide and can only be sketched in this article.

Confidentiality↗