Search PubMed⌕ Search

Biomedical subjects

N W Johnson

Publications and source records attributed to N W Johnson.

At least 91 records · Page 5Linked to original sources

Elevated conversion of alpha-2-macroglobulin to the complexed form in gingival crevicular fluid from adult periodontitis patients.

The broad spectrum protease inhibitor, alpha 2-macgrolobulin (alpha 2M), is one of the host's principal regulators of both endogenous and exogenous proteases and is likely to have an important role in the regulation of proteolytic activity at inflammatory sites. We have determined the amount of complexed (com alpha 2M) and total alpha 2M (tot alpha 2M) in gingival crevicular fluid (GCF) harvested from shallow and deep sites in adult periodontitis (AP) patients (n = 21). An ELISA technique was developed to measure both forms of alpha 2M in the same sample utilizing a monoclonal antibody (MAb) specific for the complexed form. In addition, protease activity towards human serum albumin (Prot1), transferrin (Prot2) and N alpha-benzoyl-L-arginine 7-amido-4-methylcoumarin-hydrochloride (BAAMc; Prot3) were determined in a second GCF sample from the same site. Plasma alpha 2M concentrations were only positively correlated (p = 0.0163) with GCF tot alpha 2M from highly inflamed sites. We observed a significant positive correlation between tot alpha 2M and proteolytic activity in GCF from deep sites but not from shallow sites (Prot1: p = 0.002; Prot2: p = 0.005). A similar correlation between tot alpha 2M and proteolytic activity was found at highly inflamed sites (Prot1: p = 0.014; Prot2: p = 0.002). A very high proportion of the tot alpha 2M in GCF was in the complexed form at both shallow (71.14% +/- 29.13) and deep sites (68.17% +/- 28.5) Com alpha 2M was positively correlated with proteolytic activity only in deep sites (Prot1: p = 0.015; Prot2: p = 0.031). Our results suggest that the concentration of tot alpha 2M in the gingival crevice is positively associated with the amount of proteolytic activity at the site and that protease activities in GCF may only partly explain the high percentage conversion alpha 2M to the complexed form. The high level of alpha 2M inactivation in GCF from AP patients reported here may have significance not only in view of its role as a broad spectrum protease inhibitor but also through the differential effects of native vs complexed alpha 2M on the regulation of immune responses.

Adult↗

'Oral Hygiene'.

Explore the source record for details and available documents.

Dental Caries↗

Incompleteness of oral cancer registration in south-east England, 1971-87.

Our objective was to examine the accuracy of reporting oral cancer cases to the cancer registry system. We examined a series of 583 patients with oral malignancies treated at several institutions and reported by our laboratory during 1971-87. Using patient details and pathology diagnosis, we traced the entries for these patients in the Thames Cancer Registry (TCR). Of the 583 patients identified 351 were eligible for entry in TCR. Of these, 255 were traced in the Registry and 96 were not (27%). The data, when separated for the period 1971-80 and post-1980, showed that for the earlier period under-reporting was 21% and for the later period 36%: Underascertainment was particularly marked in the mid-1980s while regional registration in the North Thames Regions was being discontinued and taken over by TCR. The major factors contributing to under-reporting are thought to be the fact that many specialised dental units and oral pathology laboratories may fail to be included in the cancer registration process and possible inconsistencies in death-initiated registrations related to this site. Similar levels of under-reporting were observed in another regional registry (South Western), suggesting that this may be a national problem. If this is the case, national incidence rates for mouth cancer may have been underestimated by about 25% during this period. This contrasts with over 90% completeness of registration for cancers as a whole.

Age Factors↗

Association of overexpression of p53 oncoprotein with the state of cell proliferation in oral carcinoma.

p53 is a nuclear phosphoprotein recognised as important in the regulation of normal cell growth and proliferation, the wild-type protein suppressing cell division. Expression of presumptive mutant protein, detected by immunohistochemistry, is used increasingly as a diagnostic and prognostic marker in human neoplasms. A question arises as to whether or not p53 (over)expression in a lesion is any more or less informative than other markers of cell proliferation. Twenty well-differentiated oral squamous cell carcinomas which had earlier been examined for immunoreactivity against a panel of p53 antibodies were examined for the status of cell proliferation--both in islands of invading neoplastic cells and in the non-malignant epithelial margins. The status of epithelial cell proliferation was found to be significantly higher in p53-positive tumours when enumerated by Ki-67 antibody, both within the tumour as well as its margins. This may confer a growth advantage to these neoplasms and reflect a status of inactivated p53 protein, although the actual cause of the rapid proliferation may lie in activation/inactivation of other genes. The PCNA labelling indices, on the other hand, were closely similar in both p53-positive and -negative groups, suggesting that stabilisation of p53 protein does not influence the proliferative advantage in these carcinomas via a deregulation step of PCNA-related gene products.

Antibodies, Monoclonal↗

Role of areca nut in the causation of oral submucous fibrosis: a case-control study in Pakistan.

A case-control study on chewing and smoking habits and oral submucous fibrosis (OSF) was undertaken in Karachi in 1989/90. Cases were patients detected with fibrous bands and leathery mucosa and hospital-based controls were matched by age and sex. Information on habits was collected by personal interview of 157 cases and 157 controls. Despite overall female preponderance, a substantial number of young men were enlisted. The male/female risks were found to be similar. Immigrants from India to Pakistan (Mohajir) had a similar risk status to local Punjabis. No differences between risks were found when comparing the three age categories, 21, 21-40, 41-60 yr. Among the cases, an increased risk was observed for areca nut chewing. This habit when practised alone appeared to have the highest risk (RR 154), followed by pan with or without tobacco (RR 64, 32 respectively). Logistic regression and discriminant analysis showed that daily consumption rates appeared to be more important with respect to risk than lifetime duration of habit. Tobacco habits were more prevalent amongst those 15 cases who presented with concurrent carcinoma and OSF: We conclude that areca nut chewing has a causal relationship with OSF: additional tobacco insult may be necessary for subsequent carcinoma development.

Adult↗

Preventive therapy for periodontal diseases.

Rational approaches to the prevention of destructive periodontitis should be based on a clear understanding of etiology and pathogenesis. However, we are dealing with a heterogeneous family of diseases in which different factors operate. It is an oversimplification to regard poor oral hygiene, and hence an accumulation of non-specific dental bacterial plaque, as the major risk factor. Epidemiological evidence indicates that host factors are likely to be of overriding importance for the most severe forms. The limitations of nonspecific plaque control are therefore discussed. Specific inhibitors of virulence factors provide a logical approach, but their clinical application awaits improved knowledge. Improvement of general health and resistance to disease by proper nutrition, the avoidance of intercurrent disease, and elimination of smoking and stress-induced risk are encouraged. The genetic basis of susceptibility to periodontitis is increasingly understood, and, while gene therapy is not likely to be a practicable approach to prevention, genetic markers of risk are emerging.

Anti-Bacterial Agents↗

Low prevalence of expression of p53 oncoprotein in oral carcinomas from Sri Lanka associated with betel and tobacco chewing.

Overexpression of p53 oncoprotein has been demonstrated in a wide range of human malignancies. We have examined the p53 expression amongst 38 Sri Lankan subjects with histologically confirmed oral squamous cell carcinomas. The mean age of the subjects was 59.4 years and betel chewing with tobacco was the most common habit (84%) with a high percentage of patients smoking (63%). Buccal mucosa was the most frequently affected site (68%) with a high proportion (79%) of well differentiated carcinomas. p53 expression was examined by standard immuno-histochemical methods on frozen sections using monoclonal antibodies PAb 1801, 240 and 421. Only 4 (11%) carcinomas showed nuclear reactivity mostly in random clusters of basal neoplastic cells. The low frequency of p53 expression could be due to deletion of both alleles or to premature truncated protein products due to nonsense mutations resulting in loss of antibody recognition sites. Alternatively the much lower prevalence than reported by others could be due to differences in aetiological agents and/or genetic predisposition of this population.

Adult↗

Comparison of isotopic and immunohistochemical methods of studying epithelial cell proliferation in hamster tongue.

Our purpose was to validate different approaches to the study of cell proliferation in stratified squamous epithelia, using oral mucosa as a model. Dorsal and ventral tongue from the hamster were examined following in vivo labelling with tritiated thymidine and bromodeoxyuridine (BrdUrd), and in vitro labelling with BrdUrd. These were compared with direct immunolabelling of fixed tissue sections with monoclonal antibody PC10. For the former methods S phase cells were quantified following autoradiography or immunohistochemistry. We conclude that the proliferative status of simple, flat, lining mucosae such as ventral tongue can be derived by all three pre-labelling methods and, on average, 18-19 cells per surface millimetre length were in DNA synthesis. On the other hand dorsal tongue epithelium, which is thicker, has an undulating morphology and a complex cell renewal pattern, gives different results with the three labelling methods. In both sites the proliferating cell nuclear antigen (PCNA) index was fourfold that obtained by nucleotide labelling. This is consistent with PCNA marking proliferative cells in other phases of the cell cycle in addition to the S phase. Thus, there are potential differences between the information on proliferative status derived by PCNA immunohistochemistry and other established cell cycle markers, which need to be taken into account in the interpretation of epithelial cell kinetic data in health and disease.

Animals↗

Serum immunoglobulin G antibodies to Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Streptococcus sanguis during experimental gingivitis in young adults.

Twenty-eight young, healthy adults completed an experimental gingivitis study in which blood and clinical recordings were obtained at baseline; after a 4-week period of thorough oral hygiene; after a subsequent 3-week period of plaque accumulation; and after another 2 weeks of thorough oral hygiene. Serum immunoglobulin G antibodies against whole cells of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Streptococcus sanguis were determined using enzyme-linked immunosorbent assay. Mean serum immunoglobulin G antibody levels to P. intermedia, F. nucleatum and S. sanguis remained essentially constant during the experiment, whereas the immunoglobulin G antibodies to P. gingivalis declined during the initial period of oral hygiene and the subsequent period of plaque accumulation to an average of 84.5% of the baseline value. This reduction could be attributed to the people who developed marked gingival inflammation during the period of plaque accumulation, indicating that the systemic host response may be associated with local tissue responses to variations in oral hygiene. These people were, however, also characterized by higher initial serum immunoglobulin G responses to P. gingivalis than people who developed less pronounced gingival inflammation during the experiment. The variability and individuality noted in the host response to potential pathogens have important implications for attempts to use such measures for establishing a diagnosis or prognosis for the individual patient.

Adult↗

Nucleolar organiser region (NOR) distribution as a diagnostic marker in oral keratosis, dysplasia and squamous cell carcinoma.

Nucleolar organiser regions (NORs) were quantified from a range of oral mucosal biopsies (n = 40) consisting of benign, reactive, dysplastic and carcinomatous lesions, using silver (Ag) staining, to see if AgNOR counts were helpful in distinguishing them. Mean counts were greater in carcinomas (8.37 +/- 6.11) compared to epithelial dysplasias (5.61 +/- 4.63) or benign keratoses (4.51 +/- 2.57). Although these differences were significant, counts in each diagnostic group overlapped so much that they were of no practical value in distinguishing between individual lesions. However, the higher counts found in many carcinomas were due to dispersion of AgNORs within the nucleoplasm, so that the AgNOR type is helpful in making such a distinction. Whether those dysplastic lesions with higher and more dispersed counts represent those at greater risk of malignant transformation awaits longitudinal study.

Adult↗

Hygiene and health: the value of antiplaque agents in promoting oral health.

The improvements in human health and increased life expectancy which have come about in many societies in the past century have been due, predominantly, to improvements in hygiene--both personal and environmental. As the common oral diseases--caries and gingivitis and to some extent periodontitis--are bacterially mediated diseases, they are also amendable to control by oral hygiene. As commonly practised however, with modern diets, mechanical oral hygiene alone has limited effect on disease incidence. The supplementation of tooth brushing with chemical agents which modulate plaque metabolism and the effects of metabolites on the hard and soft tissues of the dento-gingival structures certainly has preventive and therapeutic value. This is particularly true of fluoridated dentifrices in the control of dental caries, and of dentifrices with antibacterial and anticalculus properties, such as those containing low concentrations of the phenolic compound Triclosan, in the control of gingivitis. Microbial colonisation of tooth and other body surfaces is normal and forms part of the natural defence against dangerous exogenous organisms: thus modulating or 'controlling' plaque, not eliminating it, is the purpose of oral hygiene. The goal is to maintain a microbial ecosystem consistently associated with healthy tissues.

Anti-Infective Agents, Local↗