Radio-sensitizing effect of MEK inhibition in glioblastoma in vitro and in vivo.

INTRODUCTION: Glioblastoma (GBM) is an incurable cancer type. New therapeutic options are investigated, including targeting the mitogen-activated protein kinase (MAPK) pathway using MEK inhibitors as radio-sensitizers. In this study, we investigated whether MEK inhibition via PD0325901 leads to radio-sensitization in experimental in vitro and in vivo models of GBM. MATERIALS AND METHODS: In vitro, GBM8 multicellular spheroids were irradiated with 3 fractions of 2 Gy, during 5 consecutive days of incubation with either PD0325901 or MEK-162. In vivo, we combined PD0325901 with radiotherapy in the GBM8 orthotopic mouse model, tumor growth was measured weekly by bioluminescence imaging and overall survival and toxicity were assessed. RESULTS: Regrowth and viability of spheroids monitored until day 18, showed that both MEK inhibitors had an in vitro radio-sensitizing effect. In vivo, PD0325901 concentrations were relatively constant throughout multiple brain areas and temporal PD0325901-related adverse events such as dermatitis were observed in 4 out of 14 mice (29%). Mice that were treated with radiation alone or combined with PD0325901 had significantly better survival compared to vehicle (both P < 0.005), however, no significant interaction between PD0325901 MEK inhibition and irradiation was observed. CONCLUSION: The difference between the radiotherapy-enhancing effect of PD0325901 in vitro and in vivo urges further pharmacodynamic/pharmacokinetic investigation of PD0325901 and possibly other candidate MEK inhibitors.

Influence of a triclosan toothpaste on periodontopathic bacteria and periodontitis progression in cardiovascular patients: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Triclosan/copolymer toothpaste is effective in controlling plaque and gingivitis and in slowing the progression of periodontitis. This study describes its influence on microbiological and clinical outcomes, over a 5-year period, in patients with established cardiovascular disease (CVD). MATERIAL AND METHODS: Four-hundred and thirty-eight patients were recruited from the Cardiovascular Unit at The Prince Charles Hospital, Brisbane, Australia, and randomized to triclosan or placebo groups. Six sites per tooth were examined annually for probing pocket depth and loss of attachment. These outcomes were analysed, using generalized linear modelling, in 381 patients who had measurements from consecutive examinations. Concurrent load of the periodontal pathogens Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Tannerella forsythia and Porphyromonas gingivalis was determined, using quantitative real-time PCR, in 437 patients with baseline plaque samples. Group comparisons were expressed as geometric means. The chi-square test was used to test for differences between the two groups of patients with regard to the proportion of patients with different numbers of bacterial species. RESULTS: There was no difference in general health or periodontal status between the groups at baseline. There was a significant reduction in the number of interproximal sites showing loss of attachment between examinations, by 21% on average (p < 0.01), in the triclosan group compared with the placebo group. The prevalence of patients with F. nucleatum and A. actinomycetemcomitans was high and remained relatively constant throughout the 5 years of the study. In contrast, the prevalence of T. forsythia and P. gingivalis showed more variability; however, there was no significant difference between the groups, at any time point, in the prevalence of any organism. A significant difference in the geometric means for P. gingivalis (p = 0.01) was seen at years 1 and 4, and for F. nucleatum (p = 0.01) and in the total bacterial load (p = 0.03) at year 2; however, these differences were not statistically significant following a Bonferroni correction for multiple comparisons. There was no difference between the groups in the geometric means for each organism at year 5. CONCLUSION: Within the limitations of the study, these data suggest that the use of triclosan/copolymer toothpaste significantly slowed the progression of periodontitis in patients with CVD but that it had little influence on key subgingival periodontopathic bacteria in these patients over the 5 years of the study.

High antibody levels to P. gingivalis in cardiovascular disease.

Recent evidence suggests that strain variation in the serum IgG response to Porphyromonas gingivalis occurs in periodontal disease and cardiovascular disease (CVD). This study aimed to test the hypothesis that different P. gingivalis strains would elicit different levels of IgG, depending on a patient's cardiovascular (CV) and periodontal health. For CVD patients, serum antibody levels increased significantly with increasing numbers of deep pockets for all strains of P. gingivalis, except W50 (p < 0.001). We used a two-way analysis of variance to examine differences in antibody responses across several CV and periodontal groups simultaneously. There was a significant interaction effect (p < 0.05) between periodontal status and CV status for antibody levels to ATCC33277, UQD605, and Su63. This study shows variation in strain type with respect to serum IgG response in several CV and periodontal categories, providing further support for the role of the immune response to P. gingivalis in the relationship between periodontal disease and CVD.

Progression of periodontal disease and interleukin-10 gene polymorphism.

BACKGROUND AND OBJECTIVE: Interleukin-10 is a key immunoregulatory cytokine that may be of significance in the immunopathogenesis of chronic inflammatory diseases such as periodontal disease. Molecular genetic studies have defined a number of haplotypes that may be associated with differing levels of interleukin-10 secretion. The present study investigated the possible association between interleukin-10 gene polymorphism and periodontal disease progression. MATERIAL AND METHODS: Genomic DNA was obtained from 252 adults who were part of a prospective longitudinal study on the progression of periodontal disease in a general adult Australian population. Single nucleotide polymorphisms at positions -592 and -1082 in the interleukin-10 promoter were analysed using an induced heteroduplex methodology and used to determine interleukin-10 promoter haplotypes in individual samples. Periodontitis progression was assessed by measuring probing depths and relative attachment levels at regular intervals over a 5-year period. A generalized linear model was used to analyse the data, with age, gender, smoking status, interleukin-1 genotype and Porphyromonas gingivalis included as possible confounders. RESULTS: There was a significant (p approximately 0.02) main effect of interleukin-10 haplotypes, with individuals having either the ATA/ACC or the ACC/ACC genotype experiencing around 20% fewer probing depths of >or= 4 mm compared to individuals with other genotypes. Age and smoking had significant (p < 0.001) additional effects. CONCLUSION: These data suggest that the interleukin-10 genotype contributes to the progression of periodontal disease.

A 5-year longitudinal study of Tannerella forsythia prtH genotype: association with loss of attachment.

BACKGROUND: Tannerella forsythia (previously T. forsythensis) in subgingival plaque has been recognized as a defined periodontal pathogen, but its mere presence may be insufficient for disease initiation and/or progression. The organism may produce a cysteine protease, encoded by the prtH gene, which may play a role in the transition from commensal organism to opportunistic pathogen. This study aimed to relate changes in the level of T. forsythia prtH genotype over a 5-year period to a concomitant loss of attachment. METHODS: Real-time polymerase chain reaction was used to quantify the level of the prtH gene in plaque samples from subjects with and without attachment loss (> or =2 mm in at least two sites) over a 5-year period. Clinical measures and subgingival plaque samples were obtained at yearly intervals. RESULTS: Baseline levels of the prtH genotype were significantly lower in the subjects without loss of attachment compared to those who lost attachment over 1, 2, 4, or 5 years. In the subjects with loss of attachment, the higher prtH levels at baseline were not maintained until the end of the observation period. CONCLUSION: Higher levels of the prtH genotype were associated significantly with future attachment loss.

Basic helix-loop-helix transcription factor profiling of lung tumors shows aberrant expression of the proneural gene atonal homolog 1 (ATOH1, HATH1, MATH1) in neuroendocrine tumors.

Microarray-based expression profiling studies of lung adenocarcinomas have defined neuroendocrine subclasses with poor prognosis. As neuroendocrine development is regulated by members of the achaete-scute and atonal classes of basic helix-loop-helix (bHLH) transcription factors, we analyzed lung tumors for expression of these factors. Out of 13 bHLH genes tested, 4 genes, i.e., achaete-scute complex-like 1 (ASCL1, HASH1, Mash1), atonal homolog 1 (ATOH1, HATH1, MATH1), NEUROD4 (ATH-3, Atoh3, MATH-3) and neurogenic differentiation factor 1 (NEUROD1, NEUROD, BETA2), showed differential expression among lung tumors and absent or low expression in normal lung. As expected, tumors that have high levels of ASCL1 also express neuroendocrine markers, and we found that this is accompanied by increased levels of NEUROD1. In addition, we found ATOH1 expression in 9 (16%) out of 56 analyzed adenocarcinomas and these tumors showed neuroendocrine features as shown by dopa decarboxylase mRNA expression and immunostaining for neuroendocrine markers. ATOH1 expression as well as NEUROD4 was observed in small cell lung carcinoma (SCLC), a known neuroendocrine tumor. Since ATOH1 is not known to be involved in normal lung development, our results suggest that aberrant activation of ATOH1 leads to a neuroendocrine phenotype similar to what is observed for ASCL1 activation during normal neuroendocrine development and in lung malignancies. Our preliminary data indicate that patients with ATOH1-expressing adenocarcinomas might have a worse prognosis.

Identification and characterization of a novel luciferase-like protein in the human female reproductive tract.

A novel cDNA was cloned from human endometrium, matching a human gene with the interim name KIAA1463. An mRNA identified by 5'-rapid amplification of cDNA ends was found to be 3349 nt in length. PCR analysis also identified another transcript of 6626 nt, with an open reading frame encoding a 900 amino acid protein. A fold recognition program identified similarity to firefly luciferase containing an AMP-binding motif; hence, we refer to the predicted protein as the AMP binding/luciferase-like protein (ALLP). ALLP mRNA and protein were expressed throughout the female reproductive tract with the highest levels found in the ovary and uterus. In situ hybridization and immunohistochemistry showed predominant localization of the ALLP mRNA/protein in endometrial glandular epithelium and within the theca and granulosa cells in the ovary. In the endometrium expression of ALLP, mRNA and protein were higher during d 16-21 of the secretory phase of the cycle. Western blot analysis showed decreased expression of ALLP in the postmenopausal endometrium, and hormone replacement therapy increased the expression of ALLP. Endometrial adenocarcinoma cell lines expressed more ALLP, compared with cultured primary endometrial cells or normal endometrial tissue. The ubiquitous expression of ALLP in reproductive and nonreproductive tissues suggests that this protein, which is probably regulated by ovarian steroids, plays an important metabolic role and may be involved in such processes as implantation and tumorigenesis.

Acquisition and loss of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia over a 5-year period: effect of a triclosan/copolymer dentifrice.

OBJECTIVES: The present study describes the natural history of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia over a 5-year period and the effect of a triclosan/copolymer dentifrice on these organisms in a normal adult population. MATERIAL AND METHODS: Subgingival plaque samples were collected from 504 adult volunteers. Probing pocket depths (PPD) and relative attachment levels were measured using an automated probe. Participants were matched for disease status (CPI), plaque index, age and gender, and allocated to receive either a triclosan/copolymer or placebo dentifrice. Re-examination and subgingival plaque sampling was repeated after 1, 2, 3, 4 and 5 years. P. gingivalis, A. actinomycetemcomitans and P. intermedia were detected and quantitated using an enzyme linked immunosorbent assay. Logistic regression and generalised linear modelling were used to analyse the data. RESULTS: This 5-year longitudinal study showed considerable volatility in acquisition and loss (below the level of detection) of all three organisms in this population. Relatively few subjects had these organisms on multiple occasions. While P. gingivalis was related to loss of attachment and to PPD >/=3.5 mm, there was no relationship between A. actinomycetemcomitans or P. intermedia and disease progression over the 5 years of the study. Smokers with P. gingivalis had more PPD >/=3.5 mm than smokers without this organism. There was no significant effect of the triclosan dentifrice on P. gingivalis or A. actinomycetemcomitans. Subjects using triclosan were more likely to have P. intermedia than those not using the dentifrice; however this did not translate into these subjects having higher levels of P. intermedia and its presence was uniform showing no signs of increasing over the course of the study. CONCLUSION: The present 5-year longitudinal study has shown the transient nature of colonisation with P. gingivalis, A. actinomycetemcomitans and P. intermedia in a normal adult population. The use of a triclosan-containing dentifrice did not lead to an overgrowth of these organisms. The clinical effect of the dentifrice would appear to be independent of its antimicrobial properties.

The effect of a triclosan-containing dentifrice on the progression of periodontal disease in an adult population.

OBJECTIVES: The aim of the present study was to determine the effect of unsupervised, long-term use of a 0.3% triclosan/2% copolymer dentifrice on the progression of periodontal disease in a general adult population. METHODS: Five hundred and four volunteers were enrolled in a double-blind, controlled clinical trial. Participants were matched for disease status, plaque index, age and gender. At the baseline examination, probing pocket depths and relative attachment levels were recorded and participants were assigned to either the test or control group. Re-examinations took place after 6, 12, 24, 36, 48 and 60 months. Subgingival plaque samples were collected at each examination and assayed for Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia. A generalised linear model was used to analyse the data, with a number of covariates thought to influence the responses included as the possible confounding effects. RESULTS: The triclosan/copolymer dentifrice had a significant effect in subjects with interproximal probing depths > or =3.5 mm, where it significantly reduced the number of sites with probing depths > or =3.5 mm at the following examination, when compared with the control group (p<0.001). Furthermore, this effect increased with increasing numbers of affected sites. There was no effect of the triclosan/copolymer dentifrice in individuals without probing depths > or =3.5 mm at the previous examination. Other factors significantly affecting probing pocket depths (PPD) included increasing age, smoking and presence of P. gingivalis. PPD > or =3.5 mm were positively associated with loss of attachment some 2 years later. CONCLUSION: This study showed that in a normal adult population, unsupervised use of a triclosan/copolymer dentifrice is effective in slowing the progression of periodontal disease.

Effect of ethylene vinyl acetate (EVA) closed cell foam on transmitted forces in mouthguard material.

OBJECTIVES: To compare transmitted forces through ethylene vinyl acetate (EVA) mouthguard material and the same EVA material with gas inclusions in the form of a closed cell foam. METHOD: EVA mouthguard materials with and without foam gas inclusions and 4 mm thick were impacted with a constant force from an impact pendulum. Various porosity levels in the foam materials were produced by 1%, 5%, and 10% by weight foaming agent. The forces transmitted through the EVA after energy absorption by the test materials were measured with a force sensor and compared. RESULTS: Only minor non-significant differences in transmitted forces through the EVA with and without foam were shown. CONCLUSIONS: The inclusion of gas in the form of a closed cell foam in 4 mm thick EVA mouthguard materials did not improve the impact performance of the EVA mouthguard material.

Beneficial effects of air inclusions on the performance of ethylene vinyl acetate (EVA) mouthguard material.

OBJECTIVE: To investigate the impact characteristics of an ethylene vinyl acetate (EVA) mouthguard material with regulated air inclusions, which included various air cell volumes and wall thickness between air cells. In particular, the aim was to identify the magnitude and direction of forces within the impacts. METHOD: EVA mouthguard material, 4 mm thick and with and without air inclusions, was impacted with a constant force impact pendulum with an energy of 4.4 J and a velocity of 3 m/s. Transmitted forces through the EVA material were measured using an accelerometer, which also allowed the determination of force direction and magnitude within the impacts. RESULTS: Statistically significant reductions in the transmitted forces were observed with all the air inclusion materials when compared with EVA without air inclusions. Maximum transmitted force through one air inclusion material was reduced by 32%. Force rebound was eliminated in one material, and reduced second force impulses were observed in all the air inclusion materials. CONCLUSION: The regulated air inclusions improved the impact characteristics of the EVA mouthguard material, the material most commonly used in mouthguards world wide.

A longitudinal study of interleukin-1 gene polymorphisms and periodontal disease in a general adult population.

BACKGROUND: Cross-sectional studies have demonstrated that a specific polymorphism (allele 2 of both IL-1A +4845 and IL-1B +3954) in the IL-1 gene cluster has been associated with an increased susceptibility to severe periodontal disease and to an increased bleeding tendency during periodontal maintenance. The aim of the present study was to investigate the relationship between IL-1 genotype and periodontitis in a prospective longitudinal study in an adult population of essentially European heritage. METHODS: From an ongoing study of the Oral Care Research Programme of The University of Queensland, 295 subjects consented to genotyping for IL-1 allele 2 polymorphisms. Probing depths and relative attachment levels were recorded at baseline, 6, 12, 24, 36, 48 and 60 months using the Florida probe. Periodontitis progression at a given site was defined as attachment loss > or =2 mm at any observation period during the 5 years of the study and the extent of disease progression determined by the number of sites showing attachment loss. Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia were detected using ELISA. RESULTS: 38.9% of the subjects were positive for the composite IL-1 genotype. A relationship between the IL-1 positive genotype and increased mean probing pocket depth in non-smokers greater than 50 years of age was found. Further, IL-1 genotype positive smokers and genotype positive subjects with P. gingivalis in their plaque had an increase in the number of probing depths > or =3.5 mm. There was a consistent trend for IL-1 genotype positive subjects to experience attachment loss when compared with IL-1 genotype negative subjects. CONCLUSION: The results of this study have shown an interaction of the IL-1 positive genotype with age, smoking and P. gingivalis which suggests that IL-1 genotype is a contributory but non-essential risk factor for periodontal disease progression in this population.

Distribution of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in an Australian population.

BACKGROUND/AIM: The present study describes (i) the natural distribution of the three putative periodontopathogens Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans in an Australian population and (ii) the relationship between these organisms, pocket depths and supragingival plaque scores. METHODS: Subgingival plaque was collected from the shallowest and deepest probing site in each sextant of the dentition. In total, 6030 subgingival plaque samples were collected from 504 subjects. An ELISA utilising pathogen-specific monoclonal antibodies was used to quantitate bacterial numbers. RESULTS: : A. actinomycetemcomitans was the most frequently detected organism (22.8% of subjects) followed by P. gingivalis and P. intermedia (14.7% and 9.5% of subjects respectively). The majority of infected subjects (83%) were colonised by a single species of organism. A. actinomycetemcomitans presence was over-represented in the youngest age group but under-represented in the older age groups. Conversely, P. gingivalis and P. intermedia presence was under-represented in the youngest age group but over-represented in the older age groups. Differing trends in the distribution of these bacteria were observed between subjects depending upon the site of the infection or whether a single or mixed infection was present; however, these differences did not reach significance. Bacterial presence was strongly associated with pocket depth for both A. actinomycetemcomitans and P. gingivalis. For A. actinomycetemcomitans, the odds of a site containing this bacterium decrease with deeper pockets. In contrast, for P. gingivalis the odds of a site being positive are almost six times greater for pockets >3 mm than for pockets < or =3 mm. These odds increase further to 15.3 for pockets deeper than 5 mm. The odds of a site being P. intermedia positive were marginally greater (1.16) for pockets deeper than 3 mm. CONCLUSIONS: This cross-sectional study in a volunteer Australian population, demonstrated recognised periodontal pathogens occur as part of the flora of the subgingival plaque. Prospective longitudinal studies are needed to examine the positive relationship between pocket depth and pathogen presence with periodontal disease initiation and/or progression.

The Human Achaete Scute Homolog 2 gene contains two promotors, generating overlapping transcripts and encoding two proteins with different nuclear localization.

Placental development involves control by the basic helix-loop-helix transcription factor Mash2. Transcript analysis of the Human Achaete Scute Homolog 2 (HASH2) mRNA revealed the presence of two overlapping transcripts in first trimester placentae. The two transcripts (2.6 and 1.5 kb) are generated by two promotors which are separated by 1.1 kb, generating transcripts 1 and 2, respectively. Surprisingly, in transcript 1 which shows a broad expression, a second potential coding region, tentatively called Human Achaete Scute Associated Protein (HASAP) was present. Transcript 2 contains the HASH2 encoding region only. Analysis of protein expression from both transcripts by transfection studies with eGFP fusion proteins, revealed that both coding regions are translated from their endogenous translation initiation site and showed that both proteins are transported to the nucleus. HASH2 is distributed throughout the nucleus but the HASAP protein is transported into nuclear compartments, the nucleoli. In addition, the HASAP protein lacks the bHLH domain and bears no homology to known proteins. Moreover, allele-specific RT-PCR showed the human gene not to be subject to imprinting, possibly reflecting the biallelic expression of one of both transcripts. Our data indicate a species-specific difference between mouse and human expression of the Achaete Scute Homolog 2 and suggests a dual function of the human homologue.

Allelic IGF2R repression does not correlate with expression of antisense RNA in human extraembryonic tissues.

In the mouse, expression of an antisense Igf2r RNA (Air) is correlated with Igf2r repression on the paternal allele. One of the possible models for Igf2r repression could be through promoter competition or through the action of the Air RNA, in, e.g., transcriptional interference or repressor binding. These models predict the conservation of AIR RNA in human samples with monoallelic IGF2R expression and the production of AIR RNA in first-trimester human tissues. However, by strand-specific RT-PCR and by ribonuclease protection assay we have not detected any AIR RNA in first-trimester placental tissue samples, not even in samples that downregulate IGF2R expression in an allele-specific manner. This indicates that in contrast to the mouse, allelic IGF2R repression in the developing human placenta does not correlate with AIR expression.

The effect on energy absorption of hard inserts in laminated EVA mouthguards.

One of the suggestions for using laminated mouthguards is the inclusion of hard inserts to improve mouthguard performance. However, there is a paucity of published material on the use of such inserts and this study was designed to investigate this theory. Hard layers of ethylene vinyl acetate (EVA) were included in laminated mouthguard sheets which were then subject to repeated impacts with an impact rig. Hard inserts resulted in reduced energy absorption when compared with a control sheet of the same material and approximate thickness but without the hard inserts. Additionally, the further the hard inserts were located from the impact surface, the least reduction there was on energy absorption.

Ante-dependence modeling in a longitudinal study of periodontal disease: the effect of age, gender, and smoking status.

BACKGROUND: It is generally accepted that periodontal disease progresses by a series of bursts that are interspersed by periods of stability or even gain of attachment. In order to analyze longitudinal data on a patient's disease experience, it is necessary to use models which accommodate serial dependence. Ante-dependence between the results of a series of periodontal examinations over time can be modeled using a Markov chain. This model describes temporal changes in patients' levels of disease in terms of transition probabilities, which allow for both regression and progression of the disease. The aim of the present study was to demonstrate the use of a Markov chain model to analyze data from a longitudinal study investigating the progression of periodontal disease in an adult population. METHODS: The study population consisted of 504 volunteers; however, only 456 were included in the analysis because the remaining 48 subjects did not give consecutive data. Subjects were examined at baseline, 6 months, and 1, 2, and 3 years. Probing depths (PD) were recorded using an automated probe. Disease was defined as four or more sites with PD > or = 4 mm. Markov chain modeling was used to determine the effect of age, gender, and smoking on the natural progression and regression (healing) of periodontal disease. RESULTS: Smoking and increasing age had no effect on the progression of disease in this population, but did have a significant effect (P values < or = 0.05) in reducing the regression of disease; i.e., their effect on disease appears to be inhibition of the natural healing process. Gender had no significant effects. CONCLUSIONS: These results demonstrate how ante-dependence modeling of longitudinal data can reveal effects that may not be immediately apparent from the data, with smoking and increasing age being seen to inhibit the healing process rather than promote disease progression.

The proportion of interleukin-4, interferon-gamma and interleukin-10-positive cells in Porphyromonas gingivalis--specific T-cell lines established from P. gingivalis-positive subjects.

T-cell cytokine profiles in ten adult periodontitis and seven age-matched healthy or gingivitis subjects were determined. Porphyromonas gingivalis-specific T-cell lines were established from the peripheral blood of these individuals all of whom had past or present evidence of P. gingivalis infection. FACS analysis was used to determine the percentage of CD4- and CD8-positive cells in each line staining for cytoplasmic interleukin (IL)-4, interferon-gamma and IL-10. There were no differences in the mean percentage of IL-4-, interferon-gamma- or IL-10-positive T cells between the two groups. However, the individual profiles showed that the CD4 cells in five of the seven healthy or gingivitis lines had a higher proportion of interferon-gamma-positive cells, with two lines demonstrating higher percentages of IL-10- and/or IL-4-positive CD4 cells. Five of the ten adult periodontitis lines demonstrated either equal or higher percentages of IL-4-positive and/or IL-10-positive CD4 cells. With respect to the CD8 cells, two of the seven lines established from the healthy or gingivitis subjects and six of the ten adult periodontitis lines showed profiles with a higher percentage IL-4- and/or IL-10-positive cells. When the total T-cell contribution (CD4 plus CD8) for each T-cell line was determined from the individual CD4:CD8 ratios, only one of the healthy or gingivitis lines showed a profile with a higher proportion of IL-10-positive cells, while the results for the adult periodontitis lines were the same as indicated for the CD4 cell profiles, with five lines showing a higher percentage of IL-4- and/or IL-10-positive cells. In conclusion, this study has shown that in P. gingivalis-responsive T-cell lines established from adult periodontitis and healthy or gingivitis subjects, there was a predominant trend towards a higher percentage of interferon-gamma positive cells than either IL-4- or IL-10-positive cells. However, there were variations from this trend, although whether these variations indicate true susceptibility to progressive disease has yet to be determined.

Effect of increased community and professional awareness of plaque control on the management of inflammatory periodontal diseases.

Data from CPITN studies indicate that severe periodontitis affects approximately 10 per cent of most populations. These data have remained static for a number of years. Of interest, however, is that despite the dramatic increase in the use of oral hygiene aids, efforts by the dental profession in oral hygiene instruction, and the associated general improvement in oral hygiene levels in the community, the incidence of severe chronic inflammatory periodontal disease has remained largely unaffected. The effects of changing oral hygiene may be reflected in slight shifts in the mild and moderate classifications of periodontal disease but the prevalence of advanced disease in presumably susceptible subjects has remained relatively unchanged. The ramifications of relatively non-specific plaque control measures in the management of advanced disease in susceptible subjects are still unclear and it may not be until the adoption of a more specific approach to the control of specific pathogens which inhabit the subgingival biofilm that major changes in the general incidence of the severe inflammatory periodontal diseases will be seen.