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Biomedical subjects

M Gough

Publications and source records attributed to M Gough.

At least 37 records · Page 2Linked to original sources
PubMed1999

Apoptosis or necrosis for tumor immunotherapy: what's in a name?

Here we discuss how the mechanisms by which tumor cells are killed in vivo by gene transfer affects their immunogenicity. Our own work has shown that necrotic cell death induces immunological activation signals which recruit, load, activate and mature appropriate subsets of antigen-presenting cells. In contrast, for apoptotic cell death to be immunogenic, signals additional to cell death alone must be provided within the milieu of the dying tumor. Our conclusion is that the immunogenicity of tumor killing is determined by a combination of factors, including the mechanism of killing, the levels of cell death, the local environment that exists within the dying tumor and, as a result, the nature of the immune/scavenger cells which are present at the time of antigen release. Knowledge of how these factors can influence the immune system and lead to the breaking of tolerance to tumor-associated antigens, can potentially be exploited in the design of effective immunotherapies for cancer using gene transfer.

Animals↗
PubMed1999

Optimal education techniques for basic surgical trainees: lessons from education theory.

"Calmanisation" of surgical training and the introduction of the "New Deal" on doctor's hours has led to a reduction in "in service" training and a proliferation of training courses. Little research has been done into the optimum design of these courses. Education theory has shown that individuals have optimal learning styles and that these styles tend to be generalised across professional groups. It was decided, therefore, to investigate the optimal learning styles of basic surgical trainees. A learning style inventory was used to assess the preferred learning style of 52 basic surgical trainees. The predominant learning styles (86.5%) were convergent (n = 31) or accommodative (n = 14) whilst only 5 (9.6%) assimilative and 2 (3.9%) divergent styles were detected. Convergent and accommodative learners rely principally on hands on experience and problem solving as their optimal learning technique. Given the shorter hours and duration of Basic Surgical Training, in service practical training and surgical courses should be structured accordingly.

Adult↗
PubMed1998

Influence of preformed alpha-helix and alpha-helix induction on the activity of cationic antimicrobial peptides.

One prominent class of cationic antibacterial peptides comprises the alpha-helical class, which is unstructured in free solution but folds into an amphipathic alpha-helix upon insertion into the membranes of target cells. To investigate the importance of alpha-helicity and its induction on interaction with membranes, a series of peptides was constructed based on a hybrid of moth cecropin (amino acids 1-8) and bee melittin (amino acids 1-18) peptides. The new peptides were predicted to have a high tendency to form alpha-helices or to have preformed alpha-helices by virtue of construction of a lactam bridge between glutamate and lysine side-chains at positions i and i + 4 at various locations along the primary sequence. In two examples where the use of lactam bridge constraints induced and stabilized alpha-helical structure in benign (aqueous buffer) and/or hydrophobic medium, there was a decrease in antibacterial activity relative to the linear counterparts. Thus the preformation of alpha-helix in solution was not necessarily beneficial to antimicrobial activity. In the one case where the lactam bridge did result in increased antibacterial activity (lower minimal inhibitory concentration values) it did not increase alpha-helical content in benign or hydrophobic medium. Broadly speaking, good activity of the peptides against Pseudomonas aeruginosa correlated best (r2 = 0.88) with a helican parameter which was calculated as the induction of alpha-helix in a membrane-mimicking environment divided by the alpha-helix formation under benign conditions. Interestingly, the activity of the lactam bridge peptide constructs correlated in part with alterations in bacterial outer or cytoplasmic membrane permeability.

Amino Acid Sequence↗
PubMed1998

A few good men.

Explore the source record for details and available documents.

Female↗
PubMed1996

Colonic mucins in ulcerative colitis: evidence for loss of sulfation.

Colonic tissue obtained at surgery from control individuals and patients with ulcerative colitis was used to isolate mucins and to prepare mucin glycopolypeptides by pronase digestion. These were compared with mucins labelled with [35S] sulfate and [3H]-glucosamine after organ culture tissue samples from the same patients. A significant loss of mucin sulfation was detected in the colitis patients by both metabolic labelling and chemical analysis of the glycopolypeptides. A change in the size distribution of purified mucin oligosaccharides fractionated on BioGel P6 after release by beta-elimination was seen in both radiolabelled and non-labelled colitis mucins compared with controls. Amino acid analysis of the glycopolypeptides showed a close similarity to the expected ratio of serine:threonine:proline for MUC2 and did not vary between control and colitis groups. Analysis of the mucins confirmed > 90% purity in the labelling experiments, characteristic behaviour on density gradient centrifugation and agarose gel electrophoresis in control and ulcerative colitis groups and differences in sulfation and turnover at various sites in the normal colon.

Amino Acids↗
PubMed1996

It's not science. what can science do about it?

Scholars describe science as one variety of organized human knowledge, characterized by its process that requires testing of theories in attempts to falsify them. Its products are descriptions and theories about the physical world that have withstood attempts at falsification. While some of these products will eventually have practical applications, all are initially interesting to other scientists. Other scientists use the products that are considered useful and that stand up to additional testing in their own research, they reject the products that do not survive testing, and they ignore most of them. Risk analyses produce informed predictions about the future likelihood that loss or injury will occur as a consequence of present actions. They are delivered not to scientists but to policymakers who, having invested in the analysis, want to use them in their work. Only rarely, and perhaps never, are the predictions testable, and they are accepted or rejected on other grounds. These contentions are the bases for a review of risk assessments about dioxin and low-level radiation exposures and some speculations about coming changes in risk assessment.

Dioxins↗
PubMed1996

Antiendotoxin activity of cationic peptide antimicrobial agents.

The endotoxin from gram-negative bacteria consists of a molecule lipopolysaccharide (LPS) which can be shed by bacteria during antimicrobial therapy. A resulting syndrome, endotoxic shock, is a leading cause of death in the developed world. Thus, there is great interest in the development of antimicrobial agents which can reverse rather than promote sepsis, especially given the recent disappointing clinical performance of antiendotoxin therapies. We describe here two small cationic peptides, MBI-27 and MBI-28, which have both antiendotoxic and antibacterial activities in vitro and in vivo in animal models. We had previously demonstrated that these peptides bind to LPS with an affinity equivalent to that of polymyxin B. Consistent with this, the peptides blocked the ability of LPS and intact cells to induce the endotoxic shock mediator, tumor necrosis factor (TNF), upon incubation with the RAW 264.7 murine macrophage cell line. MBI-28 was equivalent to polymyxin B in its ability to block LPS induction of TNF by this cell line, even when added 60 min after the TNF stimulus. Furthermore, MBI-28 offered significant protection in a galactosamine-sensitized mouse model of lethal endotoxic shock. This protection correlated with the ability of MBI-28 to reduce LPS-induced circulating TNF by nearly 90% in this mouse model. Both MBI-27 and MBI-28 demonstrated antibacterial activity against gram-negative bacteria in vitro and in vivo against Pseudomonas aeruginosa infections in neutropenic mice.

Animals↗
PubMed1995

A 3-year epidemiological review of burn unit admissions in Dublin, Ireland: 1988-91.

A retrospective multifactorial epidemiological study of all patients admitted to the Burns Unit, St James's Hospital, Dublin during a 3-year period from January 1988 to December 1990 was undertaken. One hundred and twenty patients were admitted. All patients were aged over 14 years. The mean patient age was 48.2 years. Males accounted for 56 per cent of admissions. The mean percentage body surface area (%BSA) burned was 24.9 per cent. Flame was the cause of burns in 60 per cent of cases and produced the most extensive lesions. The home was the most common site of injury. Almost half the patients admitted from residential institutions sustained their burns in hot baths. Those aged over 60 years sustain smaller burns but are at increased risk from thermal injury. Twenty-one per cent of burns were caused by open fires used for heating the home. The mean time in hospital was 49.9 days. Twenty-three per cent of patients died as a result of their injuries. We have identified those living in residential institutions to be at increased risk from scald burns and suggest methods by which they may be protected.

Adolescent↗
PubMed1994

Can cohort studies detect any human cancer excess that may result from exposure to dioxin? Maybe.

We use the available information about concentrations of dioxin in highly exposed humans along with estimates of the half-life of dioxin and durations of exposure to calculate lifetime average daily doses (LADDs) of dioxin in those populations. We compare those LADDs to the LADDs of dioxin used in rodent carcinogen tests, and we also compare the tissue levels of dioxin in exposed humans and the test rodents. Using the maximum likelihood estimate of the Environmental Protection Agency's (EPA) calculated potency factor for the carcinogenicity of dioxin, we calculate the number of cancers that dioxin might be expected to cause in the exposed human populations. If dioxin causes an increase in total cancers or of a common cancer such as lung cancer, the calculated expected increases in cancer are below the limit of detectability in epidemiologic studies. If, on the other hand, dioxin causes a tumor with incidence comparable to that of soft tissue sarcomas, the calculated expected increases should be detectable in dioxin-exposed chemical workers and in the Seveso population. Our calculations lead to the conclusion that the failure of epidemiology to produce convincing evidence of any chronic human health effects from dioxin probably results from the relatively low exposures experienced by humans. From our analyses, there is no reason to allude to differential sensitivities between test animals and humans to explain the lack of convincing evidence for dioxin causing human cancers.

Adult↗
PubMed1994

A review of temporary crowns and bridges.

Successful crown and bridgework relies heavily upon the precise use of temporary restorations. It is the importance of this stage in crown and bridgework, perhaps more than any other, that is so often underestimated. This article reviews the materials currently available for temporary restorations and assesses the various methods of construction.

Crowns↗
PubMed1991

The glycoconjugate content of human faeces and ileostomy effluents.

Normal human faeces and effluent from terminal ileostomies in patients with ulcerative colitis were collected. The results for ileostomy effluent given as g/24 h (mean +/- SD; n = 12) were as follows: wet weight, 897 +/- 120; total dry weight, 84 +/- 8; non-diffusible dry weight 46 +/- 5. The corresponding results for faeces (n = 6) were 104 +/- 24; 26 +/- 6; 19 +/- 5. Whereas approximately 15% of the total dry weight of ileostomy effluent appeared to consist of mucin-derived material, only trace amounts of such material could be detected in faeces.

Adult↗
PubMed1991

Human health effects: what the data indicate.

Information about the possible human health effects of dioxin is available from studies of chemical plant workers, sprayers of dioxin-contaminated herbicides, and other exposed people. No human illness, other than the skin disease chloracne, which has occurred only in highly exposed people, has been convincingly associated with dioxin. Some epidemiologic studies have suggested associations between dioxin and stomach cancer, soft tissue sarcomas, and lymphomas, but other studies, powerful enough to detect excesses of those diseases, if they exist, have not done so. With the exception of one study of chemical plant workers that reported an excess of stomach cancer, all the suggested associations of increased cancer risks and dioxin exposures are from studies of herbicide applicators. Both direct measurements of the concentrations of dioxin in the body fat of chemical plant workers and the occurrence of chloracne in those men support the conclusion that they were exposed to far greater amounts of dioxin than herbicide applicators. Therefore, if the cancers found in herbicide users were associated with dioxin, even more of those cancers would be expected among the chemical plant workers; the expected increases are not found. In short, epidemiologic studies in which dioxin exposures are known to have been high, either because of the appearance of chloracne or from measurements of dioxin in exposed people, have failed to reveal any consistent excess of cancer. In those studies that have reported associations between exposure and disease, no chloracne was reported, and there are no measurements of higher-than-background levels of dioxin in the people who are classified as exposed.

Adult↗
PubMed1991

Human exposures from dioxin in soil--a meeting report.

A 1984 risk assessment identified 1 part per billion (ppb) of dioxin in soil as a "level of concern" at Times Beach, Mo. The authors of the assessment had to rely on many assumptions in their analysis, but since that time, a number of investigators have obtained data that bear directly on estimating exposures from substances in soil. Partly because of the assumptions and partly because of the site-specific nature of their analysis, the authors of the Times Beach risk assessment cautioned against the adoption of 1 ppb as a delineator between acceptable and nonacceptable levels of contamination. Those cautions have been more frequently ignored than honored, and 1 ppb has become a de facto standard. In November 1989, the Center for Risk Management at Resources for the Future hosted 50 experts at a workshop that heard and discussed published and new research about exposure estimates and measures. The 1984 assessment identified soil ingestion by toddlers as the single most important source of exposure to dioxin in soil; it assumed that toddlers ingested 10 g soil daily. Research discussed at the workshop shows that the average child ingests about 0.04 g soil daily, but that 1 of 320 studied children ingested 5 g. These findings leave open the risk management decision about whether acceptable exposure levels should be established to protect the average child or the extreme child. Furthermore, the absence of children from commercial and industrial sites led to suggestions that higher concentrations of dioxin are acceptable in soil at such sites. Some workshop participants objected to those suggestions because of the difficulty of assuring that such sites would not revert to residential use in the future. Whether deed restrictions are sufficient to prevent such reversions was seen as an important research topic. Workshop participants repeatedly discussed the importance of site-specific data in estimating exposures: Measured half-lives of dioxin in different soils range from 18 mo to greater than 100 yr; bioavailability from various soils differs by at least 20-fold; and the amounts of soil ingested by grazing cattle can differ 20-fold depending on conditions. Workshop participants agreed upon some suggestions for research and generally favored the development of guidelines for exposure assessment that would allow consideration of site-specific information. Furthermore, they generally agreed that no single concentration should be taken as a level of concern. Instead, levels should be established that consider the planned uses of the sites.

Animals↗