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Biomedical subjects

N W Johnson

Publications and source records attributed to N W Johnson.

At least 109 records · Page 6Linked to original sources

Interleukin-1 beta (IL-1 beta) levels in gingival crevicular fluid from adults with previous evidence of destructive periodontitis. A cross sectional study.

We have estimated the levels of Interleukin-1 beta (IL-1 beta) by ELISA in gingival crevicular fluid (GCF) at 58 sites from 37 patients with adult periodontitis. GCF was collected for 5 s on filter papers and a 2nd sample was collected for 30 s 1 min later. 68/116 strips yielded detectable levels of IL-1 beta. IL-1 beta was present in both the 1st and 2nd samples at 28 sites, in the 1st only at 4 sites and in the 2nd only at 8 sites; 18 sites were below the level of detection for the assay. When the concentrations of IL-1 beta were calculated in the original volume of GCF on each strip, the mean value for positive strips was 34.16 +/- 29.45 (SD) pg/microliters with a range from 1.75 to 97.13 pg/microliters. There were no statistically significant correlations with the plaque index, bleeding index or probable crevice depth (pocket depth). The results indicate that IL-1 is present in the GCF from a proportion of sites with evidence of previous periodontal destruction.

Adult↗

Associations between volume and flow rate of gingival crevicular fluid and clinical assessments of gingival inflammation in a population of British male adolescents.

Gingival crevicular fluid (GCF) sampling was performed on 2 occasions separated by 1 year, at 2 sites in the mouths of 102 male adolescents, mean age 17.85 years. Samples were collected onto 5 filter paper strips which were sequentially applied to the mouth of the crevice over a 9-min collection period. Volume and flow rates of GCF were determined for each site and were compared with clinical measurements of plaque, gingival colour, bleeding, gingival index (GI) and pocket depth, using a general linear models (GLM) procedure. While the initial volume of GCF showed no association with any clinical measurement, there was an association between flow rate of GCF and gingival colour. The volume of GCF collected in the final, 5th sample was associated with the GI. The sample site strongly influenced all measures of GCF volume. It is proposed that the flow rate of GCF may be a better indicator of gingival inflammation than the more imprecise clinical assessments of inflammation, since GCF flow rates more precisely reflect changes in tissue permeability. The association between the final sample, collected after 9 min, and clinical measurements, was probably a reflection of the association between clinically-detectable inflammation and the susceptibility of the site to mild irritation.

Adolescent↗

Point mutations in the Ha-ras oncogene are detectable in formalin-fixed tissues of oral squamous cell carcinomas, but are infrequent in British cases.

Oncogene expression in human neoplasia has been examined extensively in the past decade. More recently the advent of the polymerase chain reaction (PCR) has facilitated studies of oncogenes and other DNA structures. Those few studies which have so far searched for oncogene changes in oral cancer have utilized frozen specimens. We report here an adaptation of the PCR technique applicable to DNA extracted from archival specimens. Our data complement recent findings that Ha-ras mutations are infrequent in oral squamous cell carcinomas among white caucasoid populations.

Carcinoma, Squamous Cell↗

Expression of p53 mutant nuclear phosphoprotein in oral carcinoma and potentially malignant oral lesions.

An immunohistochemical study of primary oral squamous cell carcinomas (n = 37) with a monoclonal antibody (PAb 1801) specific to p53 antioncogene product demonstrated nuclear overexpression of the mutant protein in 35% of cases. Those positive included carcinomas without deep invasion suggesting that p53 mutation may occur in the early stages of progression of a malignancy. This is supported by the observation that mutant protein was detectable in limited amounts in 2 cases of oral mucosal dysplasia (n = 12). None of the normal or reactive oral mucosal tissues (n = 17) were positive for p53. The presence or absence of p53 was not correlated with the site of the lesion or its degree of differentiation. Our data suggest that p53 gene mutations are commonly involved in oral cancer but are neither sufficient nor necessary for the development of malignancy. Nevertheless, as this mutation is the commonest genetic change described so far in cancers in white caucasoids, it is possible that its presence can be used as a marker of risk in a high proportion of malignant and potentially malignant oral lesions.

Carcinoma↗

Ras mutations in United Kingdom examples of oral malignancies are infrequent.

Point mutations in codons 12, 13 or 61 of the oncogenes Ha-ras, Ki-ras or N-ras have been identified in human malignancies of many types. Using the PCR (polymerase chain reaction) technique for DNA amplification in vitro and stringent probing of the amplified DNA on dot blots with a library of specific oligonucleotides, we have screened for the presence of ras mutations in oral and para-oral malignancies and some associated lesions. The material, from UK patients, consisted of 22 oral squamous-cell carcinomas including 5 neck metastases, 1 oral mucosal dysplasia, 1 proliferative verrucous leukoplakia, 1 antral and 1 tonsillar carcinoma, 1 basal-cell carcinoma, 1 salivary adenocarcinoma, 1 salivary adenoid cystic carcinoma and 1 lung adenocarcinoma metastatic to the gingiva. Genomic DNA was extracted from tissues which were fresh or preserved in liquid nitrogen. Two DNA samples contained point mutations in codon 61 of Ki-ras. One of these mutations was in the lymphocytes infiltrating a retromolar SCC. The other mutation (CAA to CAU; substitution of glutamine by histidine) was in the lung adenocarcinoma metastasis. The absence of ras mutations in the epithelium of primary oral squamous-cell carcinomas is of considerable interest as other work in our Department on Indian cases of oral carcinomas associated with chewing tobacco (quid) revealed that 35% of these had a codon 12, 13 or 61 mutation in Ha-ras. While ras activations arising from point mutations may occur in a high proportion of oral malignancies associated with chewing tobacco (quid), this was not the case in UK oral malignancies, even where tobacco was smoked.

Aged↗

Oral cancer: is it more common than cervical?

In Britain, mouth cancer is about half as common as cervical cancer, a significant level and one that deserves more attention than currently given by health care professionals, the media and the general public. If greater attention is called for in Britain, it is certainly needed worldwide. Oral/oropharyngeal cancer and cancer of the uterine cervix have comparable global averages and in some communities, oral/oropharyngeal cancer is actually more common.

Carcinoma, Squamous Cell↗

High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India.

57 primary tumour samples from Indian oral cancer patients with a 5-15 year tobacco chewing habit, were examined for mutational activation in codons 12, 13 and 61 of the H-ras, K-ras and N-ras oncogenes. The highly sensitive assay based on specific oligonucleotide hybridisation following in vitro amplification of unique sequences by polymerase chain reaction was employed. Mutations were detected in twenty (35%) of the samples and were restricted to H-ras, codons 12, 13 and 61. Two cases had concurrent mutations in codons 12 and 61. The majority of the mutations were at H-ras 61.2 (Glutamine to Arginine) and H-ras 12.2 (Glycine to Valine). Three of the less frequent mutations are apparently novel. Interestingly, eight of the samples with H-ras mutations also showed loss of wild-type H-ras, as judged by absence of signals for wild-type codons 12 or 61 on dot blots. The specific H-ras mutations in these oral malignancies associated with tobacco chewing, may represent an important example of an environmental carcinogen-induced step, in a pathway leading to malignant transformation.

Adult↗

Identification of the major surface protein antigens of Porphyromonas gingivalis using IgG antibody reactivity of periodontal case-control serum.

The identity of the major surface antigens of Porphyromonas gingivalis was investigated. Outer membranes of P. gingivalis strains W83, W50, 381 and NCTC 11843 were prepared following inactivation of the trypsin-like enzyme activity. Three proteins, molecular weight 115, 55 and 40 kDa, were major components of the outer membranes of strains W83 and W50 and were also present in strains 381 and NCTC 11834. Two proteins, 55 and 47 kDa, were released from the cells during the sonication step of the outer membrane preparation procedure. Immunoblots using preparations of P. gingivalis W83 and serum from a case-control study of adult periodontitis demonstrated higher mean antibody reactivity in the case population to all the major proteins except for the 115 kDa outer membrane protein, which was recognized equally well by both populations. We conclude that the 55, 47 and 40 kDa proteins are important surface antigens of P. gingivalis. Characterization of the structure and function of these components should lead to an improved understanding of the host-parasite interactions in adult periodontitis.

Antigens, Bacterial↗

Specific antibody responses to subgingival plaque bacteria as aids to the diagnosis and prognosis of destructive periodontitis.

We have reviewed the recent literature on the humoral immune responses to a variety of subgingival plaque bacterial species in patients with destructive periodontal diseases. We do not feel that the information presently available on the specific antibody responses to proposed pathogens such as Bacteroides gingivalis and Actinobacillus actinomycetemcomitans allows antibody responses to be diagnostic. All control subjects without periodontal destruction have antibodies to candidate pathogens but the generally higher levels in patients are not sufficiently elevated to be diagnostic. Nor can they be used to predict the initiation of disease or the onset of new episodes of destruction where disease had previously occurred. Successful treatment of patients may lead to lower levels of antibodies to some organisms, including possible pathogens, and thus support a given species in the aetiopathogenesis of disease. It appears that unsuccessful treatment may be accompanied by continuing high antibody levels to some organisms and further studies may enable this observation to be used to monitor therapy. There is some evidence from serological studies that each destructive episode may be induced by a different bacterial species or consortium. The start of studies using single antigens and the techniques of molecular biology will provide not only antibody-based diagnostic methods but also allow us to determine which bacterial antigens are virulence factors and thus the role of the antibody responses, whether protective or damaging, in the periodontal diseases.

Actinobacillus↗

Epstein-Barr virus receptors but not viral DNA are present in normal and malignant oral epithelium.

The presence and distribution of Epstein-Barr Virus receptors (EBVR's) on a range of normal (n = 18), dysplastic (n = 10) and malignant (n = 20) oral mucosa were studied by immunocytochemical methods using the monoclonal antibodies (MAb's) HB5 and B2. EBVR's were demonstrated as membrane staining of the spinous layers of normal non- and parakeratinized epithelium, indicating that EBVR's are differentiation-linked. This distribution was retained in dysplastic epithelium. Tissue from oral squamous cell carcinomas (SCC's) showed variable reactivity of only a few cells scattered randomly within the samples. Furthermore, a sensitive in situ hybridization (ISH) technique was used to determine if Epstein-Barr virus (EBV) was present in normal (n = 15) and oral squamous cell carcinoma tissue (n = 20). No EBV DNA was demonstrated within either normal or malignant epithelium, suggesting that the virus does not persist in normal oral stratified squamous epithelium nor is there any evidence for a role in oral carcinogenesis.

Adult↗

Orofacial neoplasms: global epidemiology, risk factors and recommendations for research.

This publication is an abstract of FDI Technical Report No. 36, which was accepted by the General Assembly in Singapore in September 1990. The parent document, available on application to 64 Wimpole Street, summarizes the epidemiological evidence leading to the conclusion that malignant neoplasms of the mouth and associated structures are a major and growing public health problem, worldwide. Knowledge on risk factors is summarized and recommendations are made for research priorities and preventative strategies in which the key role and responsibility of the dental profession is emphasized. The present version contains most of the original document pertinent to squamous cell carcinoma of the oral mucosa--the major neoplasm of concern--and all the final recommendations.

Adult↗

Crevicular fluid-based diagnostic tests.

A diagnostic test seeks to establish the presence or absence of a disease. Many tests also seek to determine the severity, progression, or level of activity of a disease as well as the disease's likely further progression. Crevicular fluid-based diagnostic tests for various periodontal diseases are currently attracting much interest in clinical, academic, and industrial circles. This is because existing clinical diagnostic tests have many shortcomings. By the use of these techniques it is hoped that treatment will become more effective, and that overtreatment will be avoided, thus resulting in a more cost-effective outcome. Much basic work relevant to the development of such tests is underway, covering a wide range of potential analytes, and the contributions to the referred literature in all of these areas in the past year are reviewed.

Antibody Formation↗

Detection of high-risk groups and individuals for periodontal diseases: laboratory markers based on the microbiological analysis of subgingival plaque.

Periodontal microbiology is reviewed with regard to the potential of certain characteristics to serve as markers of high risk groups or individuals for periodontal diseases. The generally accepted associations between particular organisms and the various periodontal diseases are discussed. The usefulness of various clinical study designs is reviewed. The ecology of the subgingival plaque microflora is discussed and a number of suggestions for future research are made. We have concluded that there is no monospecific aetiology to any of the various periodontal conditions. Nevertheless, we give particular attention to the role of the black-pigmented bacteroides based upon our belief that they, and Bacteroides gingivalis in particular, are fundamental to our understanding of the biology of periodontal diseases in humans and other animals. Consequently, the contribution of its various virulence factors and their potential as markers of disease susceptibility and activity is addressed.

Bacterial Physiological Phenomena↗

The role of histopathology in the diagnosis and prognosis of periodontal diseases.

The histological evaluation of surgical biopsies from affected tissues is a standard way of assessing pathological change and determining treatment in many diseases. In most forms of periodontal disease, however, this approach finds limited application. Here, we review what uses the histopathological approach has in the study and evaluation of the periodontal diseases. Current understanding of the changes in epithelial anatomy during pocket formation, the cellular composition and dynamics of the inflammatory infiltrate and the mechanisms of bone resorption and repair are reviewed from the perspective of the information available from microscopical investigation, including the uses and potential application of modern immunocytochemical methods to these questions. The usefulness of histological study of biopsy material is reassessed in the light of advances made in immunohistochemical techniques and their application to gingival inflammatory infiltrates and epithelia. Such techniques offer immediately valuable research opportunities with potential for diagnostic applications, noteably the recognition of phases of destructive activity and their differentiation from periods of effective host defence.

Gingiva↗

Statistical models for data from periodontal research.

Many factors have been hypothesised either to characterise groups and individuals at risk for periodontal disease or to be markers of periodontal breakdown. In order to identify these as associated either with disease status or progression, a statistical association between the factor and a measure of disease will have to be demonstrated. The statistical modelling of data arising from periodontal research presents special problems. These include the large number of measurements made in each subject, the large magnitude of measurement error compared to the changes in attachment level, the analysis of longitudinal studies, the lack of a measure of instantaneous rate of attachment loss and controversies over the nature of the progression of the disease. We consider statistical methods currently available in the light of these difficulties and identify areas in which further research is necessary.

Analysis of Variance↗

The protein composition of gingival crevicular fluid sampled from male adolescents with no destructive periodontitis: baseline data of a longitudinal study.

Gingival crevicular fluid (GCF) is a promising source for markers of destructive periodontal diseases activity. As the initial stage of a longitudinal study into the characterization of disease markers, GCF sampled from 104 sites in 74 adolescents was examined via sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS/PAGE). In this population, which had varying degrees of gingivitis but little evidence of destructive periodontitis, there was a highly homologous GCF protein profile. The plasma components, albumin, transferrin and IgG, were major constituents of all samples. In addition, a second group of non-plasma derived proteins, with molecular weights 37 kDa, 47 kDa, 57 kDa and 59 kDa, was also commonly detected. The high frequency of occurrence of these components suggests that they may represent products of normal turnover of the periodontal tissues. Analysis of GCF sampled from patients with progressing destructive disease revealed a different SDS/PAGE profile particularly with respect to proteins of non-plasma origin. It is anticipated that the major metabolic changes which accompany the destruction of the tissues during future disease episodes in the adolescent study population will be discernible as alterations to the GCF protein profile.

Adolescent↗

Intra-oral colonization of macaque monkeys by Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans was acquired by captive Macaca fascicularis 3 to 6 months after birth, and all monkeys aged over 6 months harbored detectable levels. This microorganism was most frequently isolated from the gingival plaque of the incisor (and other) teeth compared with other oral sites. Strains were leukotoxic by bioassay and Western blot analysis. Antibodies in macaque serum contained neutralized the leukotoxin of a human A. actinomycetemcomitans strain. High titres of maternal neutralizing anti-leukotoxin antibodies were detected in neonates; the titre then fell rapidly so that by 6 months the antibody titer was zero. Antileukotoxin antibody production was detected after 6 months of age, rapidly reaching a high level within 2 years after birth. The presence of leukotoxic strains of A. actinomycetemcomitans in the gingival region did not appear to be correlated with an increase in susceptibility to periodontal disease.

Actinobacillus↗