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Biomedical subjects

M Cullinan

Publications and source records attributed to M Cullinan.

8 recordsLinked to original sources
PubMed2005

The distribution of Tannerella forsythia in an adolescent and adult population.

BACKGROUND: The fact that Tannerella forsythia, an important periopathogen, is difficult to cultivate from mixed infections has impeded precise estimates of its distribution within a given population. In order to discern T. forsythia alone from the mixed infection of plaque, the use of sensitive 16S ribosomal RNA based polymerase chain reaction (PCR) detection is necessary. OBJECTIVES: The aim of the present study was to determine the distribution of T. forsythia in an adult and in an adolescent population. MATERIAL AND METHODS: Subgingival plaque samples were obtained from 498 Australian adults and from 228 adolescent subjects from Manchester, UK. Tannerella forsythia was detected using PCR and confirmed by restriction analysis. Semi-quantitation of the organisms was carried out using two specific primers of differing sensitivities. RESULTS: In the adolescent population, 25% were found to carry T. forsythia, albeit in relatively low numbers. In the adult population, a total of 37.8% and 11% were found to carry the organism with primer 2 and primer 1, respectively, suggesting that around 27% had between 10(3) and 10(7) organisms. Although there was an apparent increased proportion of T. forsythia positive subjects in those aged > or = 50 years, this was not statistical significant. However, T. forsythia positive male smokers showed increased disease severity compared with T. forsythia negative subjects. CONCLUSION: This study has shown that at least 25% of the adolescent population carry low numbers of T. forsythia, whereas at least 37% of adults carry the organism, with some 11% having relatively high numbers. The relationship between T. forsythia and disease progression in these populations, however, remains to be determined.

Adolescent↗
PubMed2004

Persistent colonization with Tannerella forsythensis and loss of attachment in adolescents.

Colonization with Tannerella forsythensis may characterize the conversion of periodontally healthy sites into diseased sites. This three-year study describes the prevalence of T. forsythensis and its relationship to clinical loss of attachment (LOA) in a group of adolescents considered at risk of developing early chronic periodontitis. Adolescents with (LOA+) and without (LOA-) loss of attachment were examined at baseline and 1.5 and 3 yrs subsequently. On each occasion, attachment loss was measured on selected teeth, and the presence of T. forsythensis in their subgingival plaque samples was determined by PCR. T. forsythensis prevalence in LOA+ subjects at baseline (64%) increased to 82% and 86% on subsequent examinations. In contrast, prevalence of T. forsythensis in LOA- subjects was always significantly lower (25%, 36%, and 32%, respectively). The odds of loss of attachment were 8.16 times greater in subjects infected with T. forsythensis at each examination. These results suggest that T. forsythensis is strongly associated with loss of attachment in this adolescent population.

Adolescent↗
PubMed1997

The detection of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia using an ELISA in an adolescent population with early periodontitis.

The aim of the study was to compare the occurrence and levels of A. actinomycetemcomitans, P. gingivalis, and P. intermedia in the subgingival plaque from sites with and without early periodontitis in adolescents using an ELISA. 47, 15- to 16-year-old adolescents (39 Indo-Pakistani, 8 white Caucasian) were examined for clinical attachment level, probing depth, supragingival plaque, subgingival calculus and bleeding on probing on the mesio-buccal and disto-buccal aspects of the 1st molars and the incisors. Based on the clinical data, 2 sites per subject were selected for subgingival plaque sampling 3 weeks later: in 32 subjects with loss of attachment > or = 1 mm, a diseased site (D) and a healthy comparison control site (C) were sampled; in 15 subjects in whom loss of attachment had not yet developed, 1 of the upper molar sites was selected, called the at-risk site (R), together with a C site. The presence and levels of A. actinomycetemcomitans, P. gingivalis, and P. intermedia were determined using an ELISA. The loss of attachment subgroup had significantly more pockets > or = 4 mm, subgingival calculus and bleeding on probing (p < 0.05). Significantly more of the D than C sites had P. gingivalis both at detectable and at measurable levels (p < 0.05). In subjects who had no loss in clinical attachment levels, fewer sampled sites harboured any of the suspected periodontopathogens investigated, and no significant differences were found between the R or C sites (p > 0.05). Although there was a significantly higher prevalence and extent of loss of attachment > or = 1 mm in the Indo-Pakistani subjects compared with the Caucasians (p < 0.05), no differences could be identified in the distribution of the bacteria. It is concluded that monitoring of the subgingival plaque may be useful in studies of early periodontitis in adolescents, and the role of P. gingivalis needs to be elucidated in prospective longitudinal investigations.

Adolescent↗
PubMed1996

Periodontics into the 21st century.

In recent years advances in clinical techniques and procedures such as guided tissue regeneration and implants, have dominated periodontics. However, as we move towards the 21st century, emphasis is swinging 'back to basics' with the recognition that patient susceptibility to periodontal disease determines the ultimate outcome not only of the disease process but also of the treatment undertaken. In this context attention is returning to the host response and with the advent of clonal and molecular biological techniques, new insights are being gained into the nature of host susceptibility. Previous studies have suggested that a T-cell/macrophage immunoregulatory imbalance may exist locally in the periodontitis lesion and that this imbalance may be antigen specific. More recently, T-cell subsets have been dichotomized on the basis of their cytokine profiles. In general, Th1 cells produce IL-2 and IFN-gamma while Th2 cells produce IL-4, IL-5 and IL-6. The major function of Th1 cells is to mediate delayed type hypersensitivity. In contrast the major function of Th2 cells is to provide B-cell help. A model for periodontal disease has now been developed based on this functional dichotomy which provides a framework for the study of cytokine profiles in periodontal disease. Early studies in this context have demonstrated higher proportions of IL-4 and IL-13 producing cells in periodontitis tissues together with possible variations in IL-10 production. Clonal studies have shown that the selection of a particular cytokine profile is not antigen dependent and that differences may be due to the host susceptibility although this remains to be determined.

Adolescent↗
PubMed1992

UV induction of transforming growth factor alpha in melanoma cell lines is a posttranslational event.

Low, mitogenic fluences of UVC (3.7-5.6 Jm-2) have previously been shown to cause increases of radioimmunoassayable transforming growth factor alpha (TGF alpha) in the medium and cells of cultures of melanocytes, melanoma lines, and HeLa cells (Ellem, K.A.O., Cullinan, M., Baumann, K.C., Dunstan, A.: Carcinogenesis 9:797-801, 1988). Here the cellular mechanism of this increase is explored by Northern blotting to detect any changes in TGF alpha mRNA levels, and the use of inhibitors of macromolecular synthesis to attempt to block the increase in TGF alpha protein. We were unable to detect any increase in TGF alpha mRNA levels attributable to UVC between 2 and 24 hours after irradiation. Inhibition of DNA synthesis (arabinosylcytosine, 10 microM), RNA synthesis (actinomycin D, 3 micrograms/ml; DRB 93 microM), or protein synthesis (cycloheximide, 10 micrograms/ml) failed to prevent the UVC induced increase in TGF alpha. We conclude that the UVC induction of TGF alpha is by a posttranslational mechanism. There was considerable discordance between the amount of TGF alpha protein and its mRNA in cultures of 15 different melanoma cell lines, which again emphasized that posttranscriptional mechanisms modulate the release of immunodetectable TGF alpha. We also found that the inhibitors themselves were capable of inducing an increase in TGF alpha in MM229 cultures. This suggests that the inhibitors and UV may effect the increase by a common mechanism, perhaps the activation of cell surface proteases as suggested for other stimuli (e.g., Pandiella, A., and Massagué, J.: Proc. Natl. Acad. Sci., USA 88:1726-1730, 1991) and that the response may be part of a global response to perturbation of DNA synthesis.

Cell Death↗
PubMed1988

UVR induction of TGF alpha: a possible autocrine mechanism for the epidermal melanocytic response and for promotion of epidermal carcinogenesis.

The occurrence of the epidermal growth factor homologue, transforming growth factor alpha (TGF alpha), in embryonic and neoplastic tissues suggests that it may be an oncofetal version of epidermal growth factor. A strong case is developing for TGF alpha to have an autocrine mode of action in sustaining the autonomous growth of several types of tumour. We propose that TGF alpha normally has an autocrine role not only in stimulating the growth of some fetal tissues but also with postnatal epidermal cells in response to local stimuli--in particular ultraviolet radiation (UVR). As a first step to test this hypothesis we have checked whether UVR will induce the production of TGF alpha, measured by radioimmunoassay, using a highly specific monoclonal antibody which recognizes native, biologically active human TGF alpha. We found that cultures of normal foreskin melanocytes do not produce detectable amounts of TGF alpha when grown under routine conditions, but, within 12 h of exposure to low doses of short-wavelength UVR, significant quantities of TGF alpha are produced. The UVR-induced TGF alpha is both cell associated and released into the medium of these cultures. Also, UVR has a promoting action on epidermal cells which have been initiated by carcinogenic activity. A significant part of the promoting activity may be due to autocrine stimulation of multiplication of partially transformed epidermal cells. In this regard we found that UVR induced TGF alpha in HeLa cells and all human melanoma lines so far tested. Induction was complete within 24 h of a single exposure. Dose-response curves of TGF alpha induction in a malignant melanoma cell line showed a distinctive peak of factor induced by low (2 J/m2) doses of UVR. Higher doses which inhibit [3H]thymidine incorporation resulted in lower levels of induced TGF alpha. These findings are consistent with the participation of TGF alpha as an autocrine mediator of UVR-induced tumour promotion, as well as cell multiplication, in sun-exposed skin.

Dose-Response Relationship, Radiation↗
PubMed1987

Digital image capture and analysis for split-drop micropuncture.

A method for automated image capture and analysis of shrinking drop sequences is described. The procedure can be managed by a single operator and allows estimates of proximal tubule volume flux to be calculated during the experiment. Speed of analysis is increased considerably (mean time 1.5 min per sequence) compared with previous methods. The potential exists for measurement of droplets in tubules that follow a tortuous path in the horizontal plane and further increases in capture and analysis rate would allow estimation of volume flux under non-steady state conditions. Film processing is eliminated and the removal of operator errors, bias and fatigue associated with manual measurement, coupled with the greatly reduced time required for analysis of sequences makes the shrinking drop method much more reliable and attractive.

Animals↗