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Biomedical subjects

N W Johnson

Publications and source records attributed to N W Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1989

Detection of high-risk groups and individuals for periodontal diseases: laboratory markers from analysis of gingival crevicular fluid.

Gingival crevicular fluid is regarded as a promising medium for the detection of markers of periodontal diseases activity. The collection protocols are straight forward and non-invasive and can be performed at specific sites of interest in the periodontium. Because the fluid accumulates at the gingival margin, it will contain potential markers derived not only from the host tissues and serum but also the subgingival microbial plaque, and thus an extremely broad range of candidate molecules may be investigated. However, the ability to successfully describe indicators of current disease activity and predictors of future disease is dependent not only upon the choice of the biochemical marker but also on the accurate description of the health status of the sample sites using currently available clinical and radiographic methods. Areas of study which currently show the most promise involve the analysis of host enzyme activities directed against components of the extracellular matrix, the nature of the glycosaminoglycans released into the sulcus and the concentration in gingival crevicular fluid of certain mediators of the inflammatory process, most notably prostaglandin E2.

Disease Susceptibility↗
PubMed1989

Detection of high-risk groups and individuals for periodontal diseases: laboratory markers from analysis of saliva.

The use of saliva as a source of components that may identify subjects at risk of developing destructive periodontitis, or provide markers of disease potential or activity, has been reviewed. It was concluded that bacteria, their constituents or products are unlikely to be rewarding and that host-derived salivary factors such as enzymes cannot identify risk, as deficiency states for these do not exist. Secretory IgA, plasma IgA and IgG isotype levels and specific antibodies may be associated with risk, but probably only if levels fall below those which are protective or a specific antibody response is absent. More work is needed to distinguish between monomeric and dimeric IgA antibodies and to identify IgG antibodies in longitudinal clinical studies. In general, although saliva may prove to be useful as a source of indicators of current disease activity or as a means of assessing responses to treatment, it is unlikely to provide evidence for the existence of risk factors.

Biomarkers↗
PubMed1989

Iron deficiency reduces cytochrome concentrations of mitochondria isolated from hamster cheek pouch epithelium.

The effects of iron deficiency on the aerobic pathway of energy metabolism were studied using mitochondria isolated from epithelial cells from the hamster cheek pouch. A statistically significant reduction in the concentrations of cytochromes aa3, b and c (P less than 0.05), a reduction (P = 0.064) in cytochrome cl and altered cytochrome ratios were found in the mitochondria of iron deficient compared to normal animals. State 4 respiration was demonstrated in the mitochondria of both normal and iron deficient animals but state 3 respiration could not be demonstrated; this suggests uncoupling of oxidative phosphorylation which may be an artefact associated with the separation of epithelium from its connective tissue. Nevertheless we conclude that the reduction in cytochrome concentration is a real effect of iron deficiency which may explain, at least in part, the reduction of both energy production and cell proliferation seen in oral epithelia under these conditions.

Animals↗
PubMed1989

Associations between salivary levels of Streptococcus mutans, Streptococcus sobrinus, lactobacilli, and caries experience in Kenyan adolescents.

Salivary levels of mutans streptococci (S. mutans and S. sobrinus) and lactobacilli were determined in a random sample of rural Kenyans between 15 and 19 years of age (n = 149). It is possible for the natural history of dental caries in this population to be studied since it is characterized by a limited access to conventional dental treatment. Using a short set of biochemical tests, we identified from seven to ten presumptive mutans streptococcus colonies--cultured from the saliva of each individual--to differentiate between S. mutans and S. sobrinus. No colonies resembling S. rattus (S. mutans serotype b) were isolated. Lactobacilli were identified as Gram-positive, catalase-negative rods. The mean D1-4MFS and D3-4MFS were 7.03 +/- 6.43 and 1.46 +/- 3.44, respectively. The mean mutans streptococcus and lactobacillus levels were 8.7 x 10(4) and 6.7 x 10(4), respectively. The salivary mutans streptococcus and lactobacillus levels were significantly correlated (p less than 0.01). Of the subjects, 64% harbored only S. mutans, 4% only S. sobrinus, 30% both species, and 2% neither. Lactobacilli were ubiquitous. The caries experience of the group was significantly (p less than 0.001) correlated with both the total salivary level of mutans streptococci and the salivary S. mutans levels, but not with the salivary S. sobrinus level.

Adolescent↗
PubMed1989

Detection of high-risk groups and individuals for periodontal diseases.

Though gingivitis has a prevalence of close to 100 per cent in many populations, most forms of the 'disease' are self-limiting and reversible: tooth support and function are not compromised so the public health importance of the condition is questionable. Periodontitis occurs in a number of different clinical forms which may have quite different aetiological factors and--perhaps more importantly--host predispositions. Collectively, however, these diseases result in only a minority (approximately 5-20 per cent) of most populations which have been adequately surveyed having destructive periodontitis of a 'clinically significant' degree, i.e. with pockets over 6 mm, attachment loss over 4 mm or teeth requiring extraction because of their periodontal condition alone. Indeed, current evidence shows the reasons for tooth loss, though complex, to be primarily related to caries and its sequelae (both infective and iatrogenic). Indeed, in populations without access to dental health care services most people keep most of their teeth for most of their lives. Destructive periodontitis, therefore, is not the public health problem it was until recently assumed to be. Nevertheless, a prevalence of 5-20 per cent constitutes an endemic disorder of very significant proportion. The ability to identify such individuals in advance would be a major breakthrough, as would methods for detecting the intraoral sites of those individuals susceptible to breakdown, or undergoing a phase of active and destructive periodontitis. The former may be approached by genetic and general health screening, plus measurement of immune status to relevant microbial virulence factors; the latter by microbiological, biochemical and immunological screening of oral fluids--notably gingival crevicular fluid samples on a site specific basis.

Disease Susceptibility↗
PubMed1988

Detection of high-risk groups and individuals for periodontal diseases. Systemic predisposition and markers of general health.

The evidence for systemic predisposition to periodontal diseases is reviewed in relation to cellular and humoral immunity, drug therapy, diet and nutrition and stress. It is concluded that, apart from defects of polymorphonuclear leukocytes (PMN) and Ehlers-Danlos Syndrome, little firm evidence exists for other diseases, though insulin-dependent diabetes and acquired immune deficiency syndrome (AIDS) may accelerate and/or potentiate the damage of existing disease. The precise rôle of drugs, diet and nutrition and stress remain to be elucidated, but recent advances in these areas offer the prospect of assessing risk using carefully controlled studies.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Detection of high-risk groups and individuals for periodontal diseases. Evidence for the existence of high-risk groups and individuals and approaches to their detection.

It is argued that the periodontal diseases can no longer be regarded as universally prevalent conditions to which all members of the world's population are at equal risk if they fail to practise good oral hygiene. Rather, they should be regarded as a range of different diseases for each of which certain individuals, which together comprise certain minority groups, are at relatively high risk. The epidemiological evidence for the existence of high-risk groups is reviewed, from which it is concluded that world-wide the prevalence of severe destructive periodontitis is of the order of only 7-15% of the adult dentate population. A working classification of the different types of gingivitis and periodontitis is offered, as is a summary of the theoretically possible approaches to the detection of high-risk groups and individuals which are explored in detail in subsequent papers. Successful identification of such individuals will permit scientifically valid, rational and targetted prevention and treatment.

Adult↗
PubMed1988

Detection of high-risk groups and individuals for periodontal diseases. Clinical assessment of the periodontium.

The fundamental concepts of measuring periodontal diseases and the interpretation of such information as an historical record of disease, rather than disease activity, emphasises the need for improved diagnostic and prognostic tests. Criteria for an indicator of disease activity were suggested and an index fulfilling these should allow sites to be categorised as "active", quiescent or healing, and enable one to predict the risk of future disease activity. The ability of current measurements and indices, routinely used during clinical assessments of periodontal diseases, to fulfill the suggested criteria was considered and rejected in all cases. It is concluded that clinical parameters are only capable of identifying disease retrospectively, indicating the need for longitudinal, rather than cross-sectional studies in the search for clinical and laboratory markers of disease activity and susceptibility.

Gingival Crevicular Fluid↗
PubMed1988

The total protein concentration of gingival crevicular fluid. Variation with sampling time and gingival inflammation.

The total protein concentration of gingival crevicular fluid (GCF), sampled repeatedly over a 10-min period with the minimum of physical irritation to the sulcus, was evaluated in a group of 32 healthy adolescents. The mean concentration of the 1st sample was comparable to that of normal tissue fluids and lymph, irrespective of the state of inflammation of the sample site. However, during repeated sampling, the values rose to resemble serum protein levels, except at those sites with no clinically detectable inflammation. Gel electrophoretic analysis confirmed the increasing proportion of serum-derived molecules in the more proteinaceous GCF samples. The results demonstrate the extreme sensitivity of the gingival vasculature to GCF sampling and consequently the need for accurate standardisation of GCF collection protocols. This will apply particularly when compositional data is to be normalised with respect to the total protein content or when the levels of a serum constituent are being examined.

Adolescent↗
PubMed1987

Iron deficiency depresses cell proliferation in hamster cheek pouch epithelium.

Iron deficiency anaemia was induced in hamsters by feeding a low iron diet coupled with weekly bleeding. To assess cell proliferation, the stathmokinetic agent vinblastine sulphate was administered and cell birth rates were calculated from cumulative mitotic indices. The rate was significantly reduced in epithelium from iron-deficient animals. The uptake of tritiated thymidine [( 3H]TdR) was also significantly reduced in these animals. Results of both stathmokinetic and labelling experiments indicate that cell production in the cheek pouch epithelium of iron-deficient animals is impaired.

Anemia, Hypochromic↗
PubMed1987

Potential applications of anti-keratin antibodies in oral diagnosis.

Recent progress in understanding the biology of keratins together with the development of monoclonal antibodies to individual keratin proteins provide the foundation for studying keratin expression in normal and pathological oral epithelia. Areas of oral pathology in which the examination of epithelial keratin profiles may yield information of potential diagnostic value are discussed. Examples of altered keratin expression in epithelial dysplasia, oral cancer and odontogenic cysts and tumours are presented. Immunocytochemical demonstration of individual keratins can clarify the composition of complex epithelia and may help to establish epithelial lineage or indicate progression changes in tumours. Some problems in the application and interpretation of keratin immunocytochemistry are also considered.

Antibodies, Monoclonal↗
PubMed1987

Preclinical biochemical pharmacology and toxicology of piritrexim, a lipophilic inhibitor of dihydrofolate reductase.

Piritrexim (PTX), 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidin e, formerly called BW 301U, is a potent small-molecule inhibitor of dihydrofolate reductase (DHFR) that enters cells rapidly by passive diffusion and thus does not depend upon the transport-mediated uptake that can limit cell entry of methotrexate (MTX). PTX is as active as MTX in inhibiting DHFR and mammalian cell growth. In vivo, PTX is active against Walker 256, L1210, P388, Sarcoma 180, and Ehrlich ascites tumors. After iv administration of [14C]PTX to rats, the elimination profile of intact drug from plasma was first order with a half-life (t1/2) of 38 minutes. PTX penetrates extensively into tissues and its tissue:plasma concentration ratios are generally 10-fold higher than those reported for MTX. When administered systemically, PTX inhibits the DHFR-dependent conversion of sepiapterin or 7,8-dihydrobiopterin (BH2) to tetrahydrobiopterin (BH4), demonstrating that PTX enters brain at pharmacologically relevant concentrations. Pharmacokinetic studies in the dog indicated a mean plasma t1/2 (after iv dose) of 2.15 hours, total body clearance of 0.625 liters/hr/kg and steady-state volume of distribution of 1.82 liters/kg; the absolute bioavailability was 0.64. Toxicologic studies were conducted in rats and dogs that received daily doses for 1, 5, or 90 days. In dogs, oral doses of 480 (single dose), 25 (5 daily doses), and 2.5 mg/kg (90 daily doses) were lethal, whereas 240 (single dose), 2.5 (5 daily doses), and 0.5 mg/kg (90 daily doses) produced reversible alterations in clinical toxicity and histopathologic parameters. The lethal toxicity of PTX in dogs given 25 mg/kg/day for 5 days is prevented by oral calcium leucovorin rescue with either 0.75 or 3.0 mg/kg every hour for 4 hours on any of the 5 treatment days. The general pharmacologic profile indicates that PTX should be free of CNS, cardiovascular, and respiratory side effects at clinically useful doses.

Animals↗
PubMed1986

Changes in the rate of epithelial proliferation of rat oral mucosa in response to acute inflammation induced by turpentine.

Inflammatory lesions were produced in the buccal mucosa by a subepithelial injection of turpentine; animals were killed 24 h later, 1 h after an intravenous injection of tritiated thymidine ( [3H]-Tdr). Control rats were given [3H]-Tdr but no turpentine. Lesions comprised a turpentine pool surrounded by a dense layer of inflammatory cells, beyond which the tissues were more diffusely inflamed. The labelling index (L.I.) for mitotic activity in overlying epithelium was determined in a region (C) close to the layer of dense infiltration and in a region (D) more distant. The L.I. in region D was over four times greater than in region C, and nearly four times greater than that of the contralateral, uninjected cheek. The L.I. in the uninjected cheek was significantly lower than that in controls, which may indicate a systemic depression of proliferative activity in the experimental animals, probably due to stress. Thus mild inflammatory injury stimulates epithelial proliferation, whereas more severe inflammation depresses it, perhaps due to more extensive progenitor-cell damage.

Acute Disease↗
PubMed1986

The nature of the inflammatory infiltrates in childhood gingivitis, juvenile periodontitis and adult periodontitis: immunocytochemical studies using a monoclonal antibody to HLADr.

Routinely fixed and processed gingival biopsies from childhood gingivitis, juvenile periodontitis and chronic adult periodontitis patients have been stained immunocytochemically with a monoclonal anti HLADr antibody to aid in the identification and quantification of cell types in the inflammatory infiltrates. Using immunoperoxidase staining and morphological criteria, 9 cell types were quantified in 30 patients. Lesions in the 3 groups were found to differ widely both in size and composition. In the small childhood gingivitis lesions, most cells were small lymphocytes, over half of which were HLADr positive, whereas in juvenile periodontitis biopsies, well over half the infiltrate was plasma cells. The chronic adult periodontitis samples showed greater variability in composition between these 2 extremes, perhaps reflecting differences in disease activity. These results suggest that, when disease is quiescent, the volume of inflamed gingival connective tissue is small and is dominated by B-small lymphocytes, whilst on activation, the lesion increases in size and much of the B-lymphocyte population is transformed to plasma cells. This view corroborates the results of other workers with regard to juvenile periodontitis, but suggests a different interpretation of the quiescent lesion of childhood gingivitis from that current in the literature.

Adult↗
PubMed1985

Effects of iron deficiency on respiration of hamster cheek-pouch epithelium in vitro.

Iron-deficiency anaemia was induced in hamsters by feeding a low-iron diet coupled with weekly bleeding. Respiration, assessed by measuring oxygen uptake, was significantly reduced (p less than 0.002) in cheek-pouch epithelia from iron-deficient animals. To relate data on oxygen consumption to cell numbers, the cell densities of the basal and maturation compartments were measured. The cell density of the maturation compartment in iron-deficient animals was significantly reduced (p less than 0.05), whereas that of the basal cell compartment was marginally higher than in control animals. However, the cell density of the tissue as a whole was similar in both groups. Thus, the reduced oxygen consumption in iron deficiency was not due to a reduction in cell numbers. Although there was a significant reduction in epithelial volume in the iron-deficient group, this was not sufficient to account for the reduced oxygen uptake in cheek-pouch epithelia from these animals. It is concluded that iron-deficiency anaemia affects cell respiration directly, probably by interfering with the amounts and/or functions of iron-containing enzymes or cytochromes in the electron-transport chain.

Anemia, Hypochromic↗