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Biomedical subjects

M S Cooke

Publications and source records attributed to M S Cooke.

At least 19 recordsLinked to original sources

Comparing the attitudes of urban and rural Iranian women toward menopause.

OBJECTIVES: This study was designed to compare the attitudes of urban and rural Iranian women toward menopause. The socio-cultural context of urban Tehranian women is considerably more westernized than that of rural Semiromian women. Our original hypothesis was that urban Tehranian women would have a more negative outlook on menopause than rural women. This hypothesis was drawn from previous work implicating the youth-oriented culture of the west as responsible for the negative attitude of western women toward menopause. METHODS: A questionnaire with eight questions regarding major psychosocial issues that are of importance to menopausal women was prepared and administered to a group of 70 Tehranian and 49 Semiromian women. RESULTS: In contrast to the initial hypothesis, analysis revealed that rural Iranian women have a more negative attitude towards menopause than urban Iranian women. CONCLUSION: The more negative attitude of the rural women toward menopause in large part reflected the higher priority they placed on fertility than did their urban counterparts. Further, cross-cultural studies will illuminate exactly which social and cultural factors play a role in both the physical and psychological aspects of menopause.

Attitude to Health↗

Monoclonal antibody to single-stranded DNA: a potential tool for DNA repair studies.

Growing evidence suggests that DNA repair capacity is an important factor in cancer risk and is therefore essential to assess. Immunochemical assays are amenable to the detection of repair products in complex matrices, such as urine, facilitating noninvasive measurements, although diet and extra-DNA sources of lesion can confound interpretation. The production of single-stranded, lesion-containing DNA oligomers characterises nucleotide excision repair (NER) and hence defines the repair pathway from which a lesion may be derived. Herein we describe the characterisation of a monoclonal antibody which recognises guanine moieties in single-stranded DNA. Application of this antibody in ELISA, demonstrated such oligomers in supernatants from repair-proficient cells post-insult. Testing of urine samples from volunteers demonstrated a relationship between oligomer levels and two urinary DNA damage products, thymine dimers and 8-oxo-2'-deoxyguanosine, supporting our hypothesis that NER gives rise to lesion-containing oligomers which are specific targets for the investigation of DNA repair.

Animals↗

Laboratory evaluation of mouthguard material.

The aim of this study was to evaluate, in vitro, the EVA material (polyvinylacetate-polyethylene copolymer) most commonly used in the fabrication of mouthguards and thus to help understand mouthguard performance and to improve mouthguard design. The material was tested for tensile strength, elongation, hardness and water absorption using specimens and tests described by the American Society for Testing and Materials Standards. Standard EVA sheets of 1, 2, 3 and 5 mm thickness were prepared. With increase in the thickness of the material, both the ultimate tensile strength and the elongation were decreased. The hardness and water absorption were unaffected. It was concluded that. overall, the thicker 5 mm EVA material was recommended for mouthguards as it displayed the least deformation to load and performed equally as well in the tests as other thicknesses.

Absorption↗

The role of the mouthguard in the prevention of sports-related dental injuries: a review.

OBJECTIVES: This paper examines the literature dealing with oral-facial injuries received during participation in sport and the possibilities open to athletes for their prevention. In particular, the paper examines five different aspects of this topic: the risk of dental injury while playing sports, the role of the mouthguard in preventing injury, types of athletic mouthguard, implications for patients undergoing orthodontic treatment and behavioural aspects of mouthguard wear. RESULTS: It is clear from this review that participation in a number of sports does carry a considerable risk of sustaining dental injury, not only in the so-called contact sports such as rugby and hockey, but also in less obviously dangerous sports such as basketball. Although some evidence exists to the contrary, the majority of studies have found the mouthguard to be the most effective way of preventing such injuries. It is also clear that the custom-fabricated mouthguard, in particular the pressure-laminated variety, is seen to afford most protection. Athletes undergoing orthodontic treatment present a particular problem as they are potentially at greater risk of injury because of increased tooth mobility and the presence of orthodontic appliances. The fabrication of mouthguards for these patients is also problematic and the literature covering this is reviewed. As with other preventive measures, mouthguard usage is often less than the dental profession would like; the reasons for this are explored in a small number of studies. CONCLUSION: While much progress has been made in this area, the profession could do much more to promote the greater use of mouthguards.

Adolescent↗

Induction and excretion of ultraviolet-induced 8-oxo-2'-deoxyguanosine and thymine dimers in vivo: implications for PUVA.

Molecular epidemiology has linked ultraviolet-induced DNA damage with mutagenesis and skin carcinogenesis. Ultraviolet radiation may damage DNA in one of two ways: either directly, leading to lesions such as cyclobutane thymine dimers (T<>T), or indirectly, via photosensitizers that generate free radical species that may ultimately produce such oxidative lesions as 8-oxo-2'-deoxyguanosine. We report the results of a pilot, case control study in which seven, healthy, human volunteers (skin type II; aged 23-56 y; three male, four female) received a suberythemal dose of whole body irradiation from ultraviolet-A-emitting fluorescent tubes used in psoralen plus ultraviolet A therapy. First void, mid-stream urine samples were collected pre-exposure and daily postexposure, for up to 13 d. Analysis of urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers was by competitive enzyme-linked immunosorbent assay (interassay coefficient of variation < or = 10%) and compared with a matched, control group of unirradiated individuals. A maximal increase in levels of urinary 8-oxo-2'-deoxyguanosine was seen 4 d post-ultraviolet exposure. A subsequent reduction was noted, before finally returning to baseline. Similarly, cyclobutane thymine dimer levels peaked 3 d postexposure, before returning to baseline. In contrast to the 8-oxo-2'-deoxyguanosine analysis, however, a second peak was noted at days 9-11, before again returning to baseline. This is the first report examining urinary 8-oxo-2'-deoxyguanosine and cyclobutane thymine dimers following ultraviolet exposure of healthy human subjects. This work illustrates the induction and time course for excretion of ultraviolet-induced lesions, perhaps alluding to repair and ultimately offering the potential to define psoralen plus ultraviolet A dosage regimes in terms of minimizing DNA damage and hence cancer risk.

8-Hydroxy-2'-Deoxyguanosine↗

Aberrant processing of oxidative DNA damage in systemic lupus erythematosus.

Defective DNA damage processing has been reported in systemic lupus erythematosus (SLE). Vitamin C may modulate formation/removal of the oxidative DNA lesion 8-oxo-2'-deoxyguanosine (8-oxodG). Baseline levels of 8-oxodG measured in SLE serum, urine and PBMC DNA did not differ significantly from healthy subjects. In contrast to healthy subjects, no significant decrease in PBMC 8-oxodG or increase in urinary 8-oxodG was noted in vitamin C supplemented SLE patients. A significant, although attenuated, increase in serum 8-oxodG was detected in SLE patients, compared to healthy subjects. These data support putative abnormalities in the repair/processing of 8-oxodG in SLE.

8-Hydroxy-2'-Deoxyguanosine↗

Urinary 8-oxo-2'-deoxyguanosine--source, significance and supplements.

Oxidative damage to cellular biomolecules, in particular DNA, has been proposed to play an important role in a number of pathological conditions, including carcinogenesis. A much studied consequence of oxygen-centred radical damage to DNA is 8-oxo-2'-deoxyguanosine (8-oxodG). Using numerous techniques, this lesion has been quantified in various biological matrices, most notably DNA and urine. Until recently, it was understood that urinary 8-oxodG derives solely from DNA repair, although the processes which may yield the modified deoxynucleoside have never been thoroughly discussed. This review suggests that nucleotide excision repair and the action of a specific endonuclease may, in addition to the nucleotide pool, contribute significantly to levels of 8-oxodG in the urine. On this basis, urinary 8-oxodG represents an important biomarker of generalised, cellular oxidative stress. Current data from antioxidant supplementation trials are examined and the potential for such compounds to modulate DNA repair is considered. It is stressed that further work is required to link DNA, serum and urinary levels of 8-oxodG such that the kinetics of formation and clearance may be elucidated, facilitating greater understanding of the role played by oxidative stress in disease.

8-Hydroxy-2'-Deoxyguanosine↗

Immunochemical quantitation of UV-induced oxidative and dimeric DNA damage to human keratinocytes.

There is growing evidence to suggest that solar radiation-induced, oxidative DNA damage may play an important role in skin carcinogenesis. Numerous methods have been developed to sensitively quantitate 8-oxo-2'deoxyguanosine (8-oxodG), a recognised biomarker of oxidative DNA damage. Immunoassays may represent a means by which the limitations of many techniques, principally derived from DNA extraction and sample workup, may be overcome. We report the evaluation of probes to thymine dimers and oxidative damage in UV-irradiated cells and the DNA derived therefrom. Thymine dimers were most readily recognised, irrespective of whether in situ in cells or in extracted DNA. However, using antibody-based detection the more subtle oxidative modifications required extraction and, in the case of 8-oxodG, denaturation of the DNA prior to successful recognition. In contrast, a recently described novel probe for 8-oxodG detection showed strong recognition in cells, although appearing unsuitable for use with extracted DNA. The probes were subsequently applied to examine the relative induction of lesions in cells following UV irradiation. Guanine-glyoxal lesions predominated over thymine dimers subsequent to UVB irradiation, whereas whilst oxidative lesions increased significantly following UVA irradiation, no induction of thymine dimers was seen. These data support the emerging importance of oxidative DNA damage in UV-induced carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

Urinary thymine dimers and 8-oxo-2'-deoxyguanosine in psoriasis.

Psoralen in conjunction with UVA (PUVA) is perhaps the most effective treatment for psoriasis. It is, however, a risk factor for skin cancer in these patients and there is a need to develop non-invasive assays reflective of treatment-induced DNA damage. We report here the assessment of two important lesions, thymine dimer (T<>T) and 8-oxo-2'-deoxyguanosine (8-OHdG), in the urine of psoriasis patients. It was found that, once corrected for urine concentration, the psoriatic group had significantly higher (P<0. 0001) urinary levels of thymine dimers compared to the control group. No significant differences in urinary 8-OHdG levels were noted between the psoriatic, atopic dermatitis and control groups. Therefore biomonitoring of therapy from the very start with this simple and non-invasive assay could perhaps be an effective measure of the risk involved with the treatment allowing optimization for minimal-risk therapy.

8-Hydroxy-2'-Deoxyguanosine↗

Discrepancies in the measurement of UVC-induced 8-oxo-2'-deoxyguanosine: implications for the analysis of oxidative DNA damage.

Ultraviolet (UV) light-induced indirect, oxidative damage to DNA has received increasing attention with respect to the mutagenic and carcinogenic effects of solar radiation. An oxidative lesion that has raised particular interest because of its qualitative and quantitative importance is 8-oxo-2'-deoxyguanosine. This deoxynucleoside lesion is most frequently measured by high performance liquid chromatography with electrochemical detection (HPLC-EC) following enzymatic hydrolysis of DNA or as the base equivalent, 8-oxoguanine, by gas chromatography-mass spectrometry (GC-MS) following acid hydrolysis of DNA. We have noted a discrepancy in the literature whereby the levels of 8-oxo-2'-deoxyguanosine measured by HPLC-EC in UVC-irradiated DNA are significantly higher than when 8-oxoguanine is measured by GC-MS. By making use of the availability of both HPLC-EC and stable-isotope dilution GC-MS methodologies in our laboratory we have confirmed the discrepancy noted in the literature by parallel analysis of the same UVC-irradiated calf thymus DNA samples. Furthermore, analysis of the UVC-induced product by UV-visible spectrophotometry, voltammetry and its detection by a monoclonal antibody which recognises 8-oxo-2'-deoxyguanosine strongly suggests that the product is indeed 8-oxo-2'-deoxyguanosine. Partial explanation for this discrepancy could be an inordinate resistance of UVC-irradiated DNA to formic acid hydrolysis. However, we cannot completely exclude the possibility that there is a formic acid-labile species which co-elutes with 8-oxo-2'-deoxyguanosine in enzymatically digested UVC-irradiated DNA. Whether this phenomenon is unique to UV-irradiation damage or occurs with other systems that cause oxidative damage to DNA awaits further investigation. Irrespective of the exact mechanism, there will be significant implications for the analysis of oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

Fifteen-year reproducibility of natural head posture: A longitudinal study.

Natural head posture continues to be widely used as the logical reference position for the evaluation of craniofacial morphology. The basic underlying premise is that the long-term clinical reproducibility (variability) of natural head posture is significantly less than the variability of conventional reference planes with respect to the vertical. This study reports the 15-year longitudinal reproducibility of natural head posture. Twenty Chinese adults in Hong Kong, who had initial natural head posture radiographs at age 12 years, were followed up and had repeated cephalograms after 15 years. The method error (reproducibility) after 15 years was 2.2 degrees, which compared favorably with the 5-year reproducibility (method error = 3.0 degrees ) and the 5 to 10 minutes reproducibility (method error = 1.9 degrees ). The individual variability of natural head posture reproducibility increased slightly over time. After 15 years the variance of natural head posture (4.8 degrees [= 2.2(2)]) remains significantly less than the variance of intracranial reference planes to the vertical (25 degrees to 36 degrees ). Cephalometric analyses based on natural head posture therefore remain valid over time.

Adult↗

Comparison of cephalometric analysis using a non-radiographic sonic digitizer (DigiGraph Workstation) with conventional radiography.

Cephalometric analysis conventionally requires radiographic exposure which may not be compatible with the growing concern over radiation hazards. Recently, the Dolphin Workstation Imaging System introduced to the dental profession a non-radiographic system, called the DigiGraph Workstation which may be an alternative to cephalometric radiography. The aims of this study were to compare the validity and reproducibility of cephalometric measurements obtained from the DigiGraph Workstation with conventional cephalometric radiographs. The sample consisted of 30 human dry skulls. Two replicated sets of lateral cephalograms were obtained with steel ball markers placed at the majority of the cephalometric landmarks. Duplicate tracings prepared from each radiograph were digitized to obtain cephalometric measurements using the computer software, Dentofacial Planner. For the DigiGraph Workstation, double sonic digitizations were repeated twice for each skull, on two occasions. Fifteen angular and one linear measurements were obtained from both methods and these findings compared using ANOVA, paired t-tests and F-tests. All, except one, cephalometric measurement showed significant differences between the two methods (P < 0.0001). The DigiGraph Workstation consistently produced higher values in 11 measurements (mean differences +0.5 to +15.7 degrees or mm) and lower values in four measurements (mean differences -0.2 to -3.5 degrees). The standard deviations of the differences between readings of both methods were large (0.4-5.8 degrees or mm). The reproducibility of the DigiGraph Workstation measurements was lower than that of the radiographic measurements. The method error of the DigiGraph Workstation ranged from 7 to 70 per cent, while that of radiographic tracings was less than 2 per cent. It was concluded that measurements obtained with the DigiGraph Workstation should be interpreted with caution.

Analysis of Variance↗

Novel repair action of vitamin C upon in vivo oxidative DNA damage.

There appears to be a paucity of data examining the effect of dietary antioxidants on levels of oxidative DNA damage in vivo, limiting evidence-based assessment of antioxidant efficacy, mechanisms and recommendation for optimal intake. We have examined levels of 8-oxo-2'-deoxyguanosine (8-oxodG) in mononuclear cell DNA, serum and urine from subjects undergoing supplementation with 500 mg/day vitamin C. Significant decreases in DNA levels of 8-oxodG were seen, correlating strongly with increases in plasma vitamin C concentration. Furthermore we established a timecourse for sequential, significant increases in serum and urinary 8-oxodG levels. These results illustrate, for the first time in humans, the kinetics of 8-oxodG removal and processing in vivo, suggesting a role for vitamin C in the regulation of DNA repair enzymes and thereby demonstrating a non-scavenging antioxidant effect.

8-Hydroxy-2'-Deoxyguanosine↗

Space analysis: a comparison between sonic digitization (DigiGraph Workstation) and the digital caliper.

The introduction of the DigiGraph Workstation permits the use of sonic digitization to measure lateral cephalometric values, mesiodistal tooth size and arch perimeter discrepancy as a one-stop diagnostic record taking set-up. This study compared the reproducibility of mesiodistal total tooth widths and arch perimeter values, on plaster casts, given by the DigiGraph Workstation and by digital calipers. Forty-seven sets of plaster casts of Southern Chinese children (mean age 12.5 years) comprised the sample. Arch perimeter was measured using calipers in six segments from the distal of the first permanent molar to its antimere in each arch. The total mesiodistal widths of all teeth, excluding second and third molars, were also measured. The difference between the available arch perimeter and the total tooth widths was taken as the arch perimeter discrepancy. Sonic digitization of the study casts was completed according to instructions of the DigiGraph software. Paired t-tests and F-tests were used to compare the two methods. Compared with manual measurement, there was an over-estimation of the total tooth widths by 1 mm in the mandible and 0.5 mm in the maxilla, and an arch perimeter discrepancy of 1.6 mm in the mandible and 0.4 mm in the maxilla when using the sonic method. The sonic digitization was not as reproducible as the digital caliper and its clinical usefulness in evaluating the space problem of an individual malocclusion should be interpreted with caution.

Calibration↗

Further evidence for a possible role of conformation in the immunogenicity and antigenicity of the oxidative DNA lesion, 8-oxo-2'deoxyguanosine.

Damage to DNA by reactive oxygen species is acknowledged to be an important factor in a number of pathological conditions, including ageing and carcinogenesis. As a consequence, the development of methods for the sensitive detection and quantitation of oxidative DNA lesions has been of paramount importance. The oxidatively modified base product which has achieved most attention is 8-oxodeoxyguanosine (8-oxodG) and is a recognised marker of oxidative DNA damage. Although both polyclonal and monoclonal antibodies have previously been raised to 8-oxodG these have, for the most part failed to recognise this lesion within the DNA polymer. We have, through dilution cloning, produced a monoclonal antibody which appears to preferentially recognise 8-oxodG over deoxyguanosine (dG) in single-stranded oxidatively modified DNA. Such discrimination was not apparent when the DNA was double-stranded. Previous work has shown that 8-oxodG favours the syn glycosidic conformation due to steric repulsion, whereas dG assumes the anti. We present initial data that appear to support the postulate that it is these differences in conformation, in addition to structural recognition of the lesion itself, which are responsible for the discrimination, by our antibody of 8-oxodG over dG in single-stranded DNA.

Animals↗

The reproducibility of cephalometric landmarks: an experimental study on skulls.

Few previous cephalometric studies have used dry skulls in order to eliminate the effects of the facial soft tissues. The aim of this study were to quantify the intra-examiner reproducibility of the commonly used cephalometric landmarks, angles and distances, using dry skulls and to compare these errors with previous error data obtained from normal cephalograms of living patients. Thirty skulls were mounted in a purpose-designed holder and repeat cephalograms of each skull were recorded and digitised. All measurements were made relative to an X-Y coordinate reference grid. Scattergrams were produced to show the characteristic distribution of the intra-examiner reproducibility errors for the landmarks, and the reproducibility of the angles and distances were tabulated. This data was compared with a related study that included the soft tissue profile. The standard deviations of the skeletal and dental angles and distances were greater in the presence of the soft tissues. These differences were up to four times larger for measurements including the location of Nasion (e.g. SNA, SNB and SNPg), which was the landmark location most affected by the presence of soft tissues, and for the distance: Incisal tip of Lower Incisor to Pogonion. Anterior Nasal Spine, in the horizontal plane, was also greatly affected by the presence of the soft tissues. By using dry skulls, the errors observed in this study may serve as standards for the rational interpretation of clinical cephalometric values.

Adult↗

Immunogenicity of DNA damaged by reactive oxygen species--implications for anti-DNA antibodies in lupus.

Reactive oxygen species (ROS) are implicated in the inflammatory, autoimmune, connective tissue disease, systemic lupus erythematosus (SLE), particularly in respect of processes leading to the formation of pathological anti-DNA antibodies. Exposure to ROS increases the antigenicity of DNA for SLE antibodies, but data on the immunogenicity of ROS-DNA are not conclusive. In this study, we have examined the immunogenicity in rabbits, of DNA modified by three hydroxyl radical generating systems. Additionally, we investigated the antigenicity of UVA, UVB, and UVC irradiated DNA for lupus anti-DNA antibodies. Modification of DNA by both ROS and far UV dramatically increased its immunogenicity; the Fe2+ and H2O2 system resulted in antibodies that recognized both native and modified DNA. In our ELISA system, none of the UV antigens showed any antigenicity above native DNA for SLE sera. The data suggested that different profiles of antigenicity and immunogenicity arise dependent on the method of ROS production, but also that ROS-DNA may be a factor in antigen-driven immune complex formation in SLE.

Adult↗